Dynein Activators and Adaptors at a Glance Mara A

Home , ACTR1A, BICD2, DCTN3, DCTN6, Dynactin, Dynein

CELL SCIENCE AT A GLANCE Dynein activators and adaptors at a glance Mara A. Olenick and Erika L. F. Holzbaur*

ABSTRACT ribonucleoprotein particles for BICD2, and signaling endosomes for Cytoplasmic dynein-1 (hereafter dynein) is an essential cellular motor Hook1. In this Cell Science at a Glance article and accompanying that drives the movement of diverse cargos along the microtubule poster, we highlight the conserved structural features found in dynein cytoskeleton, including organelles, vesicles and RNAs. A long- activators, the effects of these activators on biophysical parameters, standing question is how a single form of dynein can be adapted to a such as motor velocity and stall force, and the specific intracellular wide range of cellular functions in both interphase and mitosis. functions they mediate. – Recent progress has provided new insights dynein interacts with a KEY WORDS: BICD2, Cytoplasmic dynein, Dynactin, Hook1, group of activating adaptors that provide cargo-specific and/or Microtubule motors, Trafficking function-specific regulation of the motor complex. Activating adaptors such as BICD2 and Hook1 enhance the stability of the Introduction complex that dynein forms with its required activator dynactin, leading Microtubule-based transport is vital to cellular development and to highly processive motility toward the microtubule minus end. survival. Microtubules provide a polarized highway to facilitate Furthermore, activating adaptors mediate specific interactions of the active transport by the molecular motors dynein and kinesin. While motor complex with cargos such as Rab6-positive vesicles or many types of kinesins drive transport toward microtubule plus- ends, there is only one major form of dynein, cytoplasmic dynein-1, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, which drives the trafficking of a wide array of minus-end-directed USA. cargo within the cell. Recent work has brought new insight into the spatial and temporal regulation of cytoplasmic dynein by adaptor *Author for correspondence ([email protected]) proteins, which link dynein to cargo (Fu and Holzbaur, 2014; E.L.F.H., 0000-0001-5389-4114 Kardon and Vale, 2009; Reck-Peterson et al., 2018). Interestingly, Journal of Cell Science

1 CELL SCIENCE AT A GLANCE Journal of Cell Science (2019) 132, jcs227132. doi:10.1242/jcs.227132 many of these adaptors modulate the motile properties of dynein, heads of the dynein dimer are reoriented to facilitate motility either enhancing or inhibiting movement, while some act as motility (Zhang et al., 2017); single-molecule studies have shown that the switches by co-ordinately regulating dynein and kinesin. Here, we complex between dynein–dynactin and an activating adaptor is use ‘adaptor’ as a more general term to discuss proteins that can link superprocessive compared to the motility of dynein alone dynein to cargo and use ‘activating adaptor’ or ‘activator’ to identify (McKenney et al., 2014; Schlager et al., 2014a), moving at a subclass of adaptor proteins that have been shown to enhance the velocities ranging from ∼0.4 to 1.4 µm/s over run-lengths of up to processivity of dynein. Below, and in the accompanying poster, we 40 µm. Furthermore, some activating adaptors such as Hook3 can summarize our current understanding of both the structure and recruit two dynein dimers to one dynactin complex, enhancing both function of dynein adaptor proteins. the velocity and the force produced by the motor complex (Urnavicius et al., 2018; Grotjahn et al., 2018). While it is Dynein and dynactin difficult to compare velocity and run length data across multiple Cytoplasmic dynein 1 (henceforth referred to as dynein) is a 1.4 studies due to differing experimental conditions such as buffer MDa motor complex consisting of dimerized heavy chains (DHCs; composition and ionic strength, studies that have directly compared symbol DYNC1H1), each with an N-terminal tail and a C-terminal dynein activators have found differences in velocities and force motor domain (see poster). The N-terminal tail mediates production that suggest that these cofactors can fine-tune dynein homodimerization of the heavy chains, along with binding sites motor function (McKenney et al., 2014; Olenick et al., 2016; for non-catalytic subunits, including two intermediate chains (DICs; Redwine et al., 2017; Urnavicius et al., 2018). DYNC1I1 and DYNC1I2) and two light intermediate chains (LIC1 and LIC2, also known as DYNC1LI1 and DYNC1LI2). Dynein activators Additional light chains (LCs) are also bound to the DICs. These BICD proteins were initially identified in Drosophila where non-catalytic subunits of dynein are thought to stabilize the mutations cause abnormal development of the abdomen resulting complex and may contribute to the regulation of specific dynein in a bicaudal (‘two-tailed’) phenotype (Mohler and Wieschaus, functions (recently reviewed by Reck-Peterson et al., 2018). The 1986). Drosophila BICD was found to be vital for mRNA transport motor domain of dynein is composed of six concatenated AAA+ in ribonucleoprotein (RNP) complexes and nuclear positioning domains that form a motor ring with a protruding flexible 15-nm- (Wharton and Struhl, 1989; Suter and Steward, 1991; Swan and long stalk with the microtubule-binding domain localized to the end Suter, 1996; Swan et al., 1999; Mach and Lehmann, 1997; Bullock (Gee et al., 1997; Burgess et al., 2003; Kon et al., 2011). AAA1 is and Ish-Horowicz, 2001). In mammals, there are two BICD the primary site of ATP hydrolysis, while the nucleotide state orthologs, BICD1 and BICD2, as well as two related proteins, of AAA3 has an allosteric effect on the motile properties of BICDR1 and BICDR2, which are slightly shorter. BICD proteins dynein (Takahide Kon et al., 2004; DeWitt et al., 2015; Nicholas form dimers characterized by long coiled-coil domains. Cryo-EM et al., 2015). analysis of the N-terminus of BICD2 shows an extended coiled-coil Dynein requires the co-factor dynactin, a 1 MDa, 23-subunit of ∼250 amino acid residues that extends for ∼30 nm and docks complex, the first identified activator for dynein and essential for onto the Arp1 filament of dynactin (Chowdhury et al., 2015; most cellular functions of the motor (see poster). The core of Urnavicius et al., 2015). BICD2 also interacts with the N-terminal dynactin is comprised of an ∼37-nm-long actin-like filament tail of the DHC (Chowdhury et al., 2015; Urnavicius et al., 2015) called the Arp1 filament (Schroer, 2004), which is composed of and the dynein LIC1, via coiled-coil interactions (Schroeder et al., eight Arp1 subunits (also known as ACTR1A), one β-actin 2014; Lee et al., 2018). Together, these interactions enhance the molecule and one Arp11 molecule (also known as ACTR10). affinity of the dynein–dynactin interaction (Splinter et al., 2012; Arp11 interacts with p25, p27 and p62 (also known as DCTN5, McKenney et al., 2014; Schlager et al., 2014a). While BICD2 is DCTN6 and DCTN4, respectively) to form the pointed-end mainly found in a complex with one dynein and one dynactin, complex of dynactin. The barbed end of the Arp1 filament within BICDR1 can recruit two dynein dimers to a single dynactin, which dynactin is capped by actin capping protein, a heterodimer of a further enhances the force and velocity of the motor complex CapZα and CapZβ family protein. A shoulder complex sits on the (Urnavicius et al., 2018; Grotjahn et al., 2018; Schlager et al., barbed-end, comprised of two copies of p24 (DCTN3), four 2014b). In mammalian cells, BICD proteins have been implicated copies of p50 (dynamtin or DCTN2) and two copies of p150Glued in Golgi vesicle transport via a C-terminal interaction with the (DCTN1) (Chowdhury et al., 2015; Urnavicius et al., 2015). The small GTPase Rab6 proteins (Hoogenraad et al., 2001; Matanis pointed-end of dynactin has been suggested to play a role in et al., 2002; Schlager et al., 2010; Short et al., 2002). BICD2 has facilitating cargo interaction (Zhang et al., 2011; Yeh et al., 2012; also been implicated in nuclear positioning (Splinter et al., 2012; Qiu et al., 2018) while the p150Glued subunit has an independent Hu et al., 2013). Furthermore, the C-terminal region of BICD and ATP-insensitive microtubule-binding domain (Waterman- proteins can bend back on itself to produce an autoinhibited state Storer et al., 1995). (Terawaki et al., 2015; Liu et al., 2013; Wharton and Struhl, 1989; Urnavicius et al., 2015), which can be relieved by cargo binding Activation of dynein (Liu et al., 2013; Huynh and Vale, 2017; McClintock et al., 2018; Dynein is responsible for the long-distance transport of many Sladewski et al., 2018), suggesting an efficient mechanism to cargos, some of which display highly processive motility. In vitro, regulate dynein motility. isolated or recombinant mammalian dynein is poorly processive Members of the Hook protein family activate dynein in a similar unless bound to a bead or other surface. Electron microscopy (EM) manner. There are three Hook proteins expressed in mammalian studies have indicated that in the absence of binding partners, cells, characterized by three conserved regions: a globular mammalian dynein is found in an auto-inhibited or phi state, which N-terminal Hook domain, a central coiled-coil domain that drives has a low affinity for microtubules (Torisawa et al., 2014; Zhang dimerization and forms a 31-nm helix that aligns along the Arp1 et al., 2017). In the presence of dynactin and a coiled-coil activating filament, and a divergent, predicted unstructured C-terminal domain adaptor, such as Bicaudal D (BICD) protein 2 (BICD2), the motor thought to mediate cargo binding (Walenta et al., 2001; Lee et al., Journal of Cell Science

2 CELL SCIENCE AT A GLANCE Journal of Cell Science (2019) 132, jcs227132. doi:10.1242/jcs.227132

2018; Urnavicius et al., 2018) (see poster). Hook1 and Hook3 2009). Rab11-FIP3 plays an important role in the cell-cycle- enhance the binding of dynein and dynactin to effectively activate dependent trafficking of recycling endosomes (Horgan et al., 2010; dynein motility, inducing longer run lengths and higher velocities Inoue et al., 2008; Wilson et al., 2005; Simon et al., 2008) and has than BICD2 (Olenick et al., 2016; Schroeder and Vale, 2016; been implicated in dendrite formation through trafficking of Rab11- Urnavicius et al., 2018). Complex formation requires the N-terminal and Arf6-dependent endosomal transport in neurons (Yazaki et al., Hook domain, which directly interacts with a helix of the dynein 2014; Song et al., 2015). So far, only Rab11-FIP3 has been shown subunit LIC1; this interaction is important for Hook-induced to interact with dynein, despite the high similarities between Rab11- processive motility of dynein in vitro and in cells (Lee et al., 2018; FIP3 and Rab11-FIP4 (Horgan et al., 2010; McKenney et al., 2014). Olenick et al., 2016; Schroeder and Vale, 2016). Like BICDR1, Ninein and ninein-like proteins have been identified as activating Hook3 can interact with two dimeric dynein motors per dynactin adaptors for dynein through a BioID mass spectrometry screen for (Urnavicius et al., 2018; Grotjahn et al., 2018). In mammalian cells, novel dynein–dynactin interactors (Redwine et al., 2017). These Hook2 is thought to function at the centrosome and during mitotic proteins contain a long coiled-coil stretch similar to other activators, progression (Szebenyi et al., 2007; Moynihan et al., 2009; Guthrie but have EF-hand domains similar to Rab11-FIP3 (see poster). et al., 2009; Dwivedi et al., 2019), while Hook1 and Hook3 Functionally, ninein proteins have been previously described as have been implicated in a variety of endosomal trafficking centrosomal proteins and as microtubule-anchoring factors pathways (Luiro et al., 2004; Maldonado-Báez et al., 2013; Xu (Delgehyr et al., 2005; Casenghi et al., 2003; Mogensen et al., et al., 2008; Walenta et al., 2001; Guo et al., 2016), similar to the 2000; Wang et al., 2015; Moss et al., 2007). Ninein proteins have role of fungal Hook proteins (Zhang et al., 2014; Bielska et al., been linked to trafficking, as overexpression leads to dispersion of 2014). Most recently, Hook1 has been shown to be required for the the Golgi and lysosomes (Casenghi et al., 2005). In zebrafish, loss transport of TrkB–BDNF-containing signaling endosomes in of ninein leads to defects in brain and skull development (Dauber neurons, a role specific for Hook1 but not Hook3 (Olenick et al., et al., 2012), while loss of ninein-like causes mislocalized 2019) (see poster). trafficking of cilia-directed cargo marked by Rab8a and impaired Spindly is another dynein activator which plays a role in mitosis melanosome transport (Bachmann-Gagescu et al., 2015; Dona by silencing a mitotic checkpoint after proper spindle assembly et al., 2015). (McKenney et al., 2014; Barisic et al., 2010; Griffis et al., 2007; Gassmann et al., 2010). Spindly recruits dynein to kinetochores, Candidate activators which induces the movement of chromosomes to the poles (Griffis A number of proteins have been identified as candidate activators due et al., 2007; Gassmann et al., 2008; Chan et al., 2009). Comparisons to shared structural elements found in bona fide activating adaptors, of Spindly with other dynein activators has identified two conserved but have not yet been shown to enhance processive motility of dynein features, the CC1 box and the Spindly motif (Gama et al., 2017) (see in vitro. One of these candidate activators is huntingtin-associated poster). The CC1 box is found in both Spindly and BICD proteins, protein 1 (HAP1). HAP1 interacts with huntingtin, known for its and is a segment of coiled-coil that mediates an interaction with causative role in Huntington’s disease. Huntingtin is an extended LIC1, analogous to the role of the Hook domain in Hook proteins scaffolding protein with many known interactors, one of which is the (Lee et al., 2018). In the CC1 box, mutations of two conserved intermediate chain of dynein (Caviston et al., 2007) (see poster). alanine residues to valine residues within BICD proteins causes a HAP1 also interacts with the p150Glued subunit of dynactin (Li et al., loss of interaction with dynein–dynactin in vitro (Schlager et al., 1998; Engelender et al., 1997), as well as the kinesin heavy chain and 2014b) and a loss-of-function phenotype in Drosophila (Oh et al., light chain (Twelvetrees et al., 2010; McGuire et al., 2006), 2000). Similar alanine-to-valine mutations in Spindly also resulted implicating the two proteins as having a role in intracellular in loss of dynein interaction (Gama et al., 2017). transport (Block-Galarza et al., 1997). While huntingtin has been The Spindly motif has been identified in most but not all known linked to the axonal transport of several vesicle populations dynein activators. The sequence L(F/A)xE is located just after the (Wong and Holzbaur, 2014; Gunawardena et al., 2003; Weiss and extended coiled-coil domain characteristic of validated dynein Littleton, 2016; Colin et al., 2008; Her and Goldstein, 2008), HAP1 is activators (Gama et al., 2017). This region of Spindly was found required for the huntingtin-mediated transport of autophagosomes to interact with the pointed end of dynactin. Mutation of (Wong and Holzbaur, 2014), as well as for APP trafficking the phenylalanine residue to an alanine residue caused a loss (Yang et al., 2012). It has been suggested that huntingtin and of the Spindly–dynactin interaction with dynein. However, the HAP1 together act as a platform for both dynein and kinesin phenylalanine residue is not conserved in other dynein adaptors and attachment to vesicles (Box 1), although the large size of the complex is actually an alanine residue in most cases (Gama et al., 2017). has made it difficult to dissect the underlying mechanisms through Thus, further work is required to fully define this motif and its in vitro assays. function within other dynein adaptors. Milton (in Drosophila) and TRAK1 and TRAK2 (in mammals) There are three shared elements found in experimentally belong to a family of proteins that act as motor adaptors for validated dynein activators: an extended ∼30 nm coiled-coil mitochondria. The Milton/TRAK family have an N-terminal coiled- domain, flanked at its N-terminus by a CC1 box or Hook domain, coil region with a high degree of similarity to the HAP1 domain and and at its C-terminus by a Spindly motif. These elements have also a C-terminal region that interacts with mitochondrial Rho GTPase been identified in additional proteins thought to interact with (Miro) proteins. In Drosophila, Milton in complex with Miro dynein. For example, Rab11-FIP3 shares these elements and was interacts with kinesin-1 to deliver mitochondria to neuronal also found to activate the motility of dynein (McKenney et al., synapses (Stowers et al., 2002; Glater et al., 2006). The 2014). In addition, Rab11-FIP3 contains N-terminal EF-hand mammalian homologs of Milton, TRAK1 and TRAK2, have been domains, which might act as regulatory modules. Rab11-FIP linked to dynein and kinesin motility (Box 1) and are required for proteins are mainly known to regulate the trafficking of recycling mitochondria distribution in a variety of cell types including endosomes via a conserved Rab11 GTPase-binding domain neurons (reviewed in Melkov and Abdu, 2018). TRAK1 binds

(reviewed in Horgan and McCaffrey, 2009; Jing and Prekeris, dynein–dynactin and kinesin-1, while TRAK2 predominately Journal of Cell Science

3 CELL SCIENCE AT A GLANCE Journal of Cell Science (2019) 132, jcs227132. doi:10.1242/jcs.227132

(Box 1). In Drosophila, JIP3 (also known as Sunday Driver) Box 1. Bidirectional adaptors associates with dynein–dynactin during the transport of axonal Some cargo in cells, such as mitochondria, display highly bidirectional JNK-injury signals via an endosomal pathway (Cavalli et al., motility characterized by movement toward both microtubule plus- and 2005; Abe et al., 2009). Lysosomal accumulation and maturation minus-ends, along with directional switching. Both dynein and kinesins defects have been observed in JIP3-knockout mice, consistent with are bound to some cargos, leading to the question of how overall motility previous observations in zebrafish and C. elegans (Gowrishankar is regulated. Some dynein adaptors have been suggested to act as bidirectional adaptors since they can interact directly with both dynein et al., 2017; Drerup and Nechiporuk, 2013; Edwards et al., 2013). and kinesin. In many cases, the dynein interaction region overlaps with JIP4 was shown to transport recycling endosomes during the kinesin interaction region, suggesting that the adaptor might be able cytokinesis via its interaction with kinesin-1 and dynactin, with to act as a bidirectional switch. For example, HAP1 and TRAKs have ARF6 binding acting as the regulatory switch for JIP4 interaction been reported to interact with dynein and kinesin via the HAP coiled-coil with motor proteins (Montagnac et al., 2009). However, none of domain (see poster) (McGuire et al., 2006; Twelvetrees et al., 2010; the JIPs have yet to be shown to activate dynein motility in vitro or Engelender et al., 1997; Li et al., 1998; van Spronsen et al., 2013). Furthermore, some motor adaptors have regulatory signals such as in vivo. binding partners or post-translational modifications that may mediate a controlled switch between dynein or kinesin-based motility. For example, LIS1, NDE1 and NDEL1 TRAK proteins interact with Miro, a Ca2+ sensor which alters the LIS1 (also known as PAFAH1B1) is an important regulator of association of TRAK and kinesin upon Ca2+ binding to reduce motility of dynein, first described as the gene mutated in the neurodevelopmental mitochondria (MacAskill et al., 2009; Wang and Schwarz, 2009). In disease Type 1 lissencephaly (Reiner et al., 1993). LIS1 has been addition, JIP1 has a phosphorylation site that regulates the switch from kinesin- to dynein-based motility of APP-positive vesicles (Fu and linked to the motility of vesicles, mitochondria, nuclei and Holzbaur, 2013). These bidirectional adaptors can help improve the centrosomes in a variety of organisms and cell types, so it is likely spatial and temporal targeting of cargo by regulating which motors are to be more of a global regulator of dynein motility rather than a cargo- active in response to cellular cues and demands. specific activator (Shao et al., 2013; Moughamian et al., 2013; Lenz et al., 2006; Zhang et al., 2010; Yi et al., 2011; Egan et al., 2012; Tsai et al., 2007; Xiang et al., 1995; Gambello et al., 2003). LIS1 has an N- interacts with dynein–dynactin (van Spronsen et al., 2013). In terminal dimerization domain, a coiled-coil region, a disordered loop neurons, TRAK1 is mainly localized in the axon, while TRAK2 is and a β-propeller domain with seven WD repeats (Kim et al., 2004; localized to the dendrites (van Spronsen et al., 2013; Loss and Tarricone et al., 2004) (see poster). LIS1 interacts with the homologs Stephenson, 2015), which could reflect the dependence of each NDE1 and NDEL1, which are dimeric, coiled-coil proteins that also compartment on distinct mechanisms of mitochondrial transport interact with dynein (Wang and Zheng, 2011; Zyłkiewicz et al., 2011; (see poster). Stehman et al., 2007). NDE1 and NDEL1 have both been suggested to tether LIS1 to dynein, forming a regulatory module that is Other adaptors controlled by Cdk5-dependent phosphorylation (Hebbar et al., Rab7-interacting lysosomal protein (RILP) has been suggested to link 2008; Pandey and Smith, 2011; Klinman and Holzbaur, 2015). dynein to Rab7-marked vesicles, including late endosomes and The β-propeller domain of LIS1 interacts with the dynein motor lysosomes (Cantalupo et al., 2001; Jordens et al., 2001). Biochemical domain, at the AAA3 and AAA4 modules (Huang et al., 2012; studies support a stepwise process of dynein recruitment by RILP, Toropova et al., 2014). Initial experiments suggested that LIS1 where RILP and oxysterol-binding protein-related protein 1L increases the affinity of dynein for microtubules and slows the (ORP1L, also known as OSBPL1A) form a complex with the velocity of dynein in vitro (Huang et al., 2012; McKenney et al., small GTPase Rab7 and then RILP can interact with the p150Glued 2010; Toropova et al., 2014; Yamada et al., 2008), but recent work subunit of dynactin, which in turn recruits dynein to the vesicle has challenged this idea. For yeast dynein, LIS1 is now proposed (Johansson et al., 2007). This stepwise recruitment suggests that the to induce either a weak or tight microtubule-binding state of association of dynein with vesicles can be regulated by cholesterol dynein, depending on the nucleotide bound to AAA3 and the levels, which are sensed by ORP1L. In addition, RILP has been number of LIS1 β-propeller domains (one or two) interacting with shown to self-interact, likely as a homodimer, similar to other dynein- the motor domain (DeSantis et al., 2017). In recent single- activating adaptors like BICD2 (Wu et al., 2005; Colucci et al., 2005). molecule studies using mammalian dynein in complex with However, RILP has not yet been shown to specifically activate dynactin and BICD2, LIS1 was found to increase the frequency dynein-driven motility in vitro or in cells. and velocity of dynein motility in a concentration-dependent c-Jun N-terminal kinase (JNK)-interacting proteins (JIPs) have manner (Baumbach et al., 2017; Gutierrez et al., 2017). Current also been identified as motor adaptors (see poster). There are four models suggest that the binding of LIS1 favors or stabilizes the mammalian JIPs, JIP1 to JIP4 (also known as MAPK8IP1– ‘open’ state of dynein and enhances the formation of a motile MAPK8IP3 and SPAG9, respectively) which are highly expressed dynein–dynactin-activating adaptor complex, but is not required in the brain (Dickens et al., 1997; Yasuda et al., 1999; Kelkar et al., for motility once the complex is fully assembled (see poster). 2005, 2000). Each JIP protein contains a JNK-binding domain Further studies are required to fully elucidate the mechanisms of near the N-terminus, which can interact with kinases of the JNK LIS1-dependent regulation of dynein. pathway and p38 MAPK pathway to signal for growth, differentiation and apoptosis (Whitmarsh, 2006). In addition to Conclusions signaling factors, JIPs interact with microtubule motors. All of the Great strides have been made to uncover the structure and function JIPs have been found to interact with kinesin-1 (Verhey et al., 2001; of individual dynein activators and adaptors but there is still much to Bowman et al., 2000; Montagnac et al., 2009; Fu and Holzbaur, learn about the regulation of dynein. Significant further work is 2013). JIP3 and JIP4, which each contain N-terminal coiled-coil needed to understand the specific regulatory mechanisms involved, regions (Kelkar et al., 2005, 2000), have also been implicated in how they may be co-ordinated to mediate dynein function in vivo minus-end motility via interactions with dynein and/or dynactin and how these proteins might play a role in disease states. Journal of Cell Science

4 CELL SCIENCE AT A GLANCE Journal of Cell Science (2019) 132, jcs227132. doi:10.1242/jcs.227132

Competing interests DeWitt, M. A., Cypranowska, C. A., Cleary, F. B., Belyy, V. and Yildiz, A. (2015). The authors declare no competing or financial interests. The AAA3 domain of cytoplasmic dynein acts as a switch to facilitate microtubule release. Nat. Struct. Mol. Biol. 22, 73-80. Funding Dickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L. and Davis, R. J. (1997). A cytoplasmic inhibitor Our work in this area is supported by the National Institutes of Health (NIH) (R35 of the JNK signal transduction pathway. Science 277, 693-696. GM126950) to E.L.F.H. Deposited in PMC for release after 12 months. Dona, M., Bachmann-Gagescu, R., Texier, Y., Toedt, G., Hetterschijt, L., Tonnaer, E. L., Peters, T. A., van Beersum, S. E. C., Bergboer, J. G. M., Horn, Cell science at a glance N. et al. (2015). NINL and DZANK1 co-function in vesicle transport and are A high-resolution version of the poster and individual poster panels are available essential for photoreceptor development in zebrafish. PLoS Genet. 11, e1005574. for downloading at http://jcs.biologists.org/lookup/doi/10.1242/jcs.227132. Drerup, C. M. and Nechiporuk, A. V. (2013). JNK-interacting protein 3 mediates the supplemental retrograde transport of activated c-Jun N-terminal kinase and lysosomes. PLoS Genet. 9, e1003303. References Dwivedi, D., Kumari, A., Rathi, S., Mylavarapu, S. V. S. and Sharma, M. (2019). Abe, N., Almenar-Queralt, A., Lillo, C., Shen, Z., Lozach, J., Briggs, S. P., The dynein adaptor Hook2 plays essential roles in mitotic progression and Williams, D. S., Goldstein, L. S. B. and Cavalli, V. (2009). Sunday driver cytokinesis. J. Cell Biol. 218, 871-894. interacts with two distinct classes of axonal organelles. J. Biol. Chem. 284, Edwards, S. L., Yu, S., Hoover, C. M., Phillips, B. C., Richmond, J. E. and Miller, 34628-34639. K. G. (2013). An organelle gatekeeper function for Caenorhabditis elegans UNC- Bachmann-Gagescu, R., Dona, M., Hetterschijt, L., Tonnaer, E., Peters, T., de 16 (JIP3) at the axon initial segment. Genetics 194, 143-161. Vrieze, E., Mans, D. A., van Beersum, S. E. C., Phelps, I. G., Arts, H. H. et al. Egan, M. J., Tan, K. and Reck-Peterson, S. L. (2012). Lis1 is an initiation factor for (2015). The ciliopathy protein CC2D2A associates with NINL and functions in dynein-driven organelle transport. J. Cell Biol. 197, 971-982. RAB8-MICAL3-regulated vesicle trafficking. PLoS Genet. 11, e1005575. Engelender, S., Sharp, A. H., Colomer, V., Tokito, M. K., Lanahan, A., Worley, P., Barisic, M., Sohm, B., Mikolcevic, P., Wandke, C., Rauch, V., Ringer, T., Hess, Holzbaur, E. L. F. and Ross, C. A. (1997). Huntingtin-associated protein 1 M., Bonn, G. and Geley, S. (2010). Spindly/CCDC99 is required for efficient (HAP1) interacts with the p150Glued subunit of dynactin. Hum. Mol. Genet. 6, chromosome congression and mitotic checkpoint regulation. Mol. Biol. Cell 21, 2205-2212. Fu, M. and Holzbaur, E. L. F. (2013). JIP1 regulates the directionality of APP axonal 1968-1981. Baumbach, J., Murthy, A., McClintock, M. A., Dix, C. I., Zalyte, R., Hoang, H. T. transport by coordinating kinesin and dynein motors. J. Cell Biol. 202, 495-508. Fu, M. and Holzbaur, E. L. F. (2014). Integrated regulation of motor-driven organelle and Bullock, S. L. (2017). Lissencephaly-1 is a context-dependent regulator of transport by scaffolding proteins. Trends Cell Biol. 24, 564-574. the human dynein complex. Elife 6, e21768. Gama, J. B., Pereira, C., Simões, P. A., Celestino, R., Reis, R. M., Barbosa, D. J., Bielska, E., Schuster, M., Roger, Y., Berepiki, A., Soanes, D. M., Talbot, N. J. Pires, H. R., Carvalho, C., Amorim, J., Carvalho, A. X. et al. (2017). Molecular and Steinberg, G. (2014). Hook is an adapter that coordinates kinesin-3 and mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch dynein cargo attachment on early endosomes. J. Cell Biol. 204, 989-1007. complex and Spindly. J. Cell Biol. 216, 943-960. Block-Galarza, J., Chase, K. O., Sapp, E., Vaughn, K. T., Vallee, R. B., DiFiglia, Gambello, M. J., Darling, D. L., Yingling, J., Tanaka, T., Gleeson, J. G., M. and Aronin, N. (1997). Fast transport and retrograde movement of huntingtin Wynshaw-Boris, A., Marchionni, M. and Dubois-Dalcq, M. (2003). Multiple and HAP 1 in axons. Neuroreport 8, 2247-2251. dose-dependent effects of Lis1 on cerebral cortical development. J. Neurosci. 23, Bowman, A. B., Kamal, A., Ritchings, B. W., Philp, A. V., McGrail, M., Gindhart, 1719-1729. J. G. and Goldstein, L. S. (2000). Kinesin-dependent axonal transport is Gassmann, R., Essex, A., Hu, J.-S., Maddox, P. S., Motegi, F., Sugimoto, A., mediated by the sunday driver (SYD) protein. Cell 103, 583-594. O’Rourke, S. M., Bowerman, B., McLeod, I., Yates, J. R. et al. (2008). A new Bullock, S. L. and Ish-Horowicz, D. (2001). Conserved signals and machinery for mechanism controlling kinetochore-microtubule interactions revealed by RNA transport in Drosophila oogenesis and embryogenesis. Nature 414, comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/ 611-616. Zw10 complex. Genes Dev. 22, 2385-2399. Burgess, S. A., Walker, M. L., Sakakibara, H., Knight, P. J. and Oiwa, K. (2003). Gassmann, R., Holland, A. J., Varma, D., Wan, X., Civril, F., Cleveland, D. W., Dynein structure and power stroke. Nature 421, 715-718. Oegema, K., Salmon, E. D. and Desai, A. (2010). Removal of Spindly from Cantalupo, G., Alifano, P., Roberti, V., Bruni, C. B. and Bucci, C. (2001). Rab- microtubule-attached kinetochores controls spindle checkpoint silencing in interacting lysosomal protein (RILP): the Rab7 effector required for transport to human cells. Genes Dev. 24, 957-971. – lysosomes. EMBO J. 20, 683 693. Gee, M. A., Heuser, J. E. and Vallee, R. B. (1997). An extended microtubule- ̈ Casenghi, M., Meraldi, P., Weinhart, U., Duncan, P. I., Korner, R. and Nigg, E. A. binding structure within the dynein motor domain. Nature 390, 636-639. (2003). Polo-like Kinase 1 Regulates Nlp, a centrosome protein involved in Glater, E. E., Megeath, L. J., Stowers, R. S. and Schwarz, T. L. (2006). Axonal microtubule nucleation. Dev. Cell 5, 113-125. transport of mitochondria requires milton to recruit kinesin heavy chain and is light Casenghi, M., Barr, F. A. and Nigg, E. A. (2005). Phosphorylation of Nlp by Plk1 chain independent. J. Cell Biol. 173, 545-557. negatively regulates its dynein-dynactin-dependent targeting to the centrosome. Gowrishankar, S., Wu, Y. and Ferguson, S. M. (2017). Impaired JIP3-dependent J. Cell Sci. 118, 5101-5108. axonal lysosome transport promotes amyloid plaque pathology. J. Cell Biol. 216, Cavalli, V., Kujala, P., Klumperman, J. and Goldstein, L. S. B. (2005). Sunday 3291-3305. driver links axonal transport to damage signaling. J. Cell Biol. 168, 775-787. Griffis, E. R., Stuurman, N. and Vale, R. D. (2007). Spindly, a novel protein Caviston, J. P., Ross, J. L., Antony, S. M., Tokito, M. and Holzbaur, E. L. F. essential for silencing the spindle assembly checkpoint, recruits dynein to the (2007). Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc. kinetochore. J. Cell Biol. 177, 1005-1015. Natl. Acad. Sci. USA 104, 10045-10050. Grotjahn, D. A., Chowdhury, S., Xu, Y., McKenney, R. J., Schroer, T. A. and Chan, Y. W., Fava, L. L., Uldschmid, A., Schmitz, M. H. A., Gerlich, D. W., Nigg, Lander, G. C. (2018). Cryo-electron tomography reveals that dynactin recruits a E. A. and Santamaria, A. (2009). Mitotic control of kinetochore-associated dynein team of dyneins for processive motility. Nat. Struct. Mol. Biol. 25, 203-207. and spindle orientation by human Spindly. J. Cell Biol. 185, 859-874. Gunawardena, S., Her, L.-S., Brusch, R. G., Laymon, R. A., Niesman, I. R., Chowdhury, S., Ketcham, S. A., Schroer, T. A. and Lander, G. C. (2015). Gordesky-Gold, B., Sintasath, L., Bonini, N. M. and Goldstein, L. S. B. (2003). Structural organization of the dynein-dynactin complex bound to microtubules. Disruption of axonal transport by loss of huntingtin or expression of pathogenic Nat. Struct. Mol. Biol. 22:345-347. polyQ proteins in Drosophila. Neuron 40, 25-40. Colin, E., Zala, D., Liot, G., Rangone, H., Borrell-Pages,̀ M., Li, X.-J., Saudou, F. Guo, X., Farıas,́ G. G., Mattera, R. and Bonifacino, J. S. (2016). Rab5 and its and Humbert, S. (2008). Huntingtin phosphorylation acts as a molecular switch effector FHF contribute to neuronal polarity through dynein-dependent retrieval of for anterograde/retrograde transport in neurons. EMBO J. 27, 2124-2134. somatodendritic proteins from the axon. Proc. Natl. Acad. Sci. USA 113, Colucci, A. M. R., Campana, M. C., Bellopede, M. and Bucci, C. (2005). The Rab- E5318-E5327. interacting lysosomal protein, a Rab7 and Rab34 effector, is capable of self- Guthrie, C. R., Schellenberg, G. D. and Kraemer, B. C. (2009). SUT-2 potentiates interaction. Biochem. Biophys. Res. Commun. 334, 128-133. tau-induced neurotoxicity in Caenorhabditis elegans. Hum. Mol. Genet. 18, Dauber, A., LaFranchi, S. H., Maliga, Z., Lui, J. C., Moon, J. E., McDeed, C., 1825-1838. Henke, K., Zonana, J., Kingman, G. A., Pers, T. H. et al. (2012). Novel Gutierrez, P. A., Ackermann, B. E., Vershinin, M. and McKenney, R. J. (2017). microcephalic primordial dwarfism disorder associated with variants in the Differential effects of the dynein-regulatory factor Lissencephaly-1 on processive centrosomal protein ninein. J. Clin. Endocrinol. Metab. 97, E2140-E2151. dynein-dynactin motility. J. Biol. Chem. 292, 12245-12255. Delgehyr, N., Sillibourne, J., Bornens, M. and Bornens, M. (2005). Microtubule Hebbar, S., Mesngon, M. T., Guillotte, A. M., Desai, B., Ayala, R. and Smith, D. S. nucleation and anchoring at the centrosome are independent processes linked by (2008). Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in ninein function. J. Cell Sci. 118, 1565-1575. neural stem cells. J. Cell Biol. 182, 1063-1071. DeSantis, M. E., Cianfrocco, M. A., Htet, Z. M., Tran, P. T., Reck-Peterson, S. L. Her, L.-S. and Goldstein, L. S. B. (2008). Enhanced sensitivity of striatal neurons to and Leschziner, A. E. (2017). Lis1 has two opposing modes of regulating axonal transport defects induced by mutant huntingtin. J. Neurosci. 28,

cytoplasmic dynein. Cell 170, 1197-1208.e12. 13662-13672. Journal of Cell Science

5 CELL SCIENCE AT A GLANCE Journal of Cell Science (2019) 132, jcs227132. doi:10.1242/jcs.227132

Hoogenraad, C. C., Akhmanova, A., Howell, S. A., Dortland, B. R., De Zeeuw, regulates COPI-independent Golgi–ER transport by recruiting the dynein– C. I., Willemsen, R., Visser, P., Grosveld, F. and Galjart, N. (2001). Mammalian dynactin motor complex. Nat. Cell Biol. 4, 986-992. Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by McClintock, M. A., Dix, C. I., Johnson, C. M., McLaughlin, S. H., Maizels, R. J., interacting with these complexes. EMBO J. 20, 4041-4054. Hoang, H. T. and Bullock, S. L. (2018). RNA-directed activation of cytoplasmic Horgan, C. P. and McCaffrey, M. W. (2009). The dynamic Rab11-FIPs. Biochem. dynein-1 in reconstituted transport RNPs. Elife. 7, e36312. Soc. Trans. 37, 1032-1036. McGuire, J. R., Rong, J., Li, S.-H. and Li, X.-J. (2006). Interaction of Huntingtin- Horgan, C. P., Hanscom, S. R., Jolly, R. S., Futter, C. E. and McCaffrey, M. W. associated protein-1 with kinesin light chain: implications in intracellular trafficking (2010). Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate in neurons. J. Biol. Chem 281, 3552-3559. transport to the endosomal-recycling compartment. J. Cell Sci. 123, 181-191. McKenney, R. J., Vershinin, M., Kunwar, A., Vallee, R. B. and Gross, S. P. Hu, D. J.-K., Baffet, A. D., Nayak, T., Akhmanova, A., Doye, V. and Vallee, R. B. (2010). LIS1 and NudE Induce a persistent dynein force-producing state. Cell 141, (2013). Dynein recruitment to nuclear pores activates apical nuclear migration and 304-314. mitotic entry in brain progenitor cells. Cell 154, 1300-1313. McKenney, R. J., Huynh, W., Tanenbaum, M. E., Bhabha, G. and Vale, R. D. Huang, J., Roberts, A. J., Leschziner, A. E. and Reck-Peterson, S. L. (2012). Lis1 (2014). Activation of cytoplasmic dynein motility by dynactin-cargo adapter acts as a “clutch” between the ATPase and microtubule-binding domains of the complexes. Science 345, 337-341. dynein motor. Cell 150, 975-986. Melkov, A. and Abdu, U. (2018). Regulation of long-distance transport of Huynh, W. and Vale, R. D. (2017). Disease-associated mutations in human BICD2 mitochondria along microtubules. Cell. Mol. Life Sci. 75, 163-176. hyperactivate motility of dynein-dynactin. J. Cell Biol. 216, 3051-3060. Mogensen, M. M., Malik, A., Piel, M., Bouckson-Castaing, V. and Bornens, M. Inoue, H., Ha, V. L., Prekeris, R. and Randazzo, P. A. (2008). Arf GTPase- (2000). Microtubule minus-end anchorage at centrosomal and non-centrosomal activating protein ASAP1 Interacts with Rab11 effector FIP3 and regulates sites: the role of ninein. J. Cell Sci. 113, 3013-3023. pericentrosomal localization of transferrin receptor–positive recycling endosome. Mohler, J. and Wieschaus, E. F. (1986). Dominant maternal-effect mutations of Mol. Biol. Cell 19, 4224-4237. Drosophila melanogaster causing the production of double-abdomen embryos. Jing, J. and Prekeris, R. (2009). Polarized endocytic transport: The roles of Rab11 Genetics 112, 803-822. and Rab11-FIPs in regulating cell polarity. Histol. Histopathol. 24, 1171-1180. Montagnac, G., Sibarita, J.-B., Loubéry, S., Daviet, L., Romao, M., Raposo, G. Johansson, M., Rocha, N., Zwart, W., Jordens, I., Janssen, L., Kuijl, C., and Chavrier, P. (2009). ARF6 Interacts with JIP4 to control a motor switch Olkkonen, V. M. and Neefjes, J. (2007). Activation of endosomal dynein motors mechanism regulating endosome traffic in cytokinesis. Curr. Biol. 19, 184-195. by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll Moss, D. K., Bellett, G., Carter, J. M., Liovic, M., Keynton, J., Prescott, A. R., spectrin. J. Cell Biol. 176, 459-471. Lane, E. B. and Mogensen, M. M. (2007). Ninein is released from the centrosome Jordens, I., Fernandez-Borja, M., Marsman, M., Dusseljee, S., Janssen, L., and moves bi-directionally along microtubules. J. Cell Sci. 120, 3064-3074. Calafat, J., Janssen, H., Wubbolts, R. and Neefjes, J. (2001). The Rab7 effector Moughamian, A. J., Osborn, G. E., Lazarus, J. E., Maday, S. and Holzbaur, protein RILP controls lysosomal transport by inducing the recruitment of dynein- E. L. F. (2013). Ordered recruitment of dynactin to the microtubule plus-end is dynactin motors. Curr. Biol. 11, 1680-1685. required for efficient initiation of retrograde axonal transport. J. Neurosci. 33, Kardon, J. R. and Vale, R. D. (2009). Regulators of the cytoplasmic dynein motor. 13190-13203. Nat. Rev. Mol. Cell Biol. 10, 854-865. Moynihan, K. L., Pooley, R., Miller, P. M., Kaverina, I. and Bader, D. M. (2009). Kelkar, N., Gupta, S., Dickens, M. and Davis, R. J. (2000). Interaction of a Murine CENP-F regulates centrosomal microtubule nucleation and interacts with mitogen-activated protein kinase signaling module with the neuronal protein JIP3. Hook2 at the centrosome. Mol. Biol. Cell 20, 4790-4803. Mol. Cell. Biol. 20, 1030-1043. Nicholas, M. P., Berger, F., Rao, L., Brenner, S., Cho, C. and Gennerich, A. Kelkar, N., Standen, C. L. and Davis, R. J. (2005). Role of the JIP4 scaffold protein (2015). Cytoplasmic dynein regulates its attachment to microtubules via in the regulation of mitogen-activated protein kinase signaling pathways. Mol. Cell. nucleotide state-switched mechanosensing at multiple AAA domains. Proc. Biol. 25, 2733-2743. Natl. Acad. Sci. USA 112, 6371-6376. Kim, M. H., Cooper, D. R., Oleksy, A., Devedjiev, Y., Derewenda, U., Reiner, O., Oh, J., Baksa, K. and Steward, R. (2000). Functional domains of the Drosophila Otlewski, J. and Derewenda, Z. S. (2004). The structure of the N-terminal bicaudal-D protein. Genetics 154, 713-724. domain of the product of the lissencephaly gene Lis1 and its functional Olenick, M. A., Dominguez, R. and Holzbaur, E. L. F. (2019). Dynein activator implications. Structure 12, 987-998. Hook1 is required for trafficking of BDNF-signaling endosomes in neurons. J. Cell Klinman, E. and Holzbaur, E. L. F. (2015). Stress-induced CDK5 activation Biol. 218, 220-233. disrupts axonal transport via Lis1/Ndel1/Dynein. Cell Rep. 12, 462-473. Olenick, M. A., Tokito, M., Boczkowska, M., Dominguez, R. and Holzbaur, Kon, T., Sutoh, K. and Kurisu, G. (2011). X-ray structure of a functional full-length E. L. F. (2016). Hook adaptors induce unidirectional processive motility by dynein motor domain. Nat. Struct. Mol. Biol. 18, 638-642. enhancing the Dynein-Dynactin interaction. J. Biol. Chem. 291, 18239-18251. Lee, I.-G., Olenick, M. A., Boczkowska, M., Franzini-Armstrong, C., Holzbaur, Pandey, J. P. and Smith, D. S. (2011). A Cdk5-dependent switch regulates Lis1/ E. L. F. and Dominguez, R. (2018). A conserved interaction of the dynein light Ndel1/dynein-driven organelle transport in adult axons. J. Neurosci. 31, intermediate chain with dynein-dynactin effectors necessary for processivity. Nat. 17207-17219. Commun. 9, 986. Qiu, R., Zhang, J. and Xiang, X. (2018). p25 of the dynactin complex plays a dual Lenz, J. H., Schuchardt, I., Straube, A. and Steinberg, G. (2006). A dynein role in cargo binding and dynactin regulation. J. Biol. Chem. 293, 15606-15619. loading zone for retrograde endosome motility at microtubule plus-ends. EMBO J. Reck-Peterson, S. L., Redwine, W. B., Vale, R. D. and Carter, A. P. (2018). The 25:2275-2286. cytoplasmic dynein transport machinery and its many cargoes. Nat. Rev. Mol. Cell Li, S.-H., Gutekunst, C.-A., Hersch, S. M., Li, X.-J., Sheth, A., Kim, J., Young, A., Biol. 19, 382-398. Penney, J., Golden, J., Aronin, N. et al. (1998). Interaction of huntingtin- Redwine, W. B., DeSantis, M. E., Hollyer, I., Htet, Z. M., Tran, P. T., Swanson, associated protein with dynactin P150Glued. J. Neurosci. 18, 1261-1269. S. K., Florens, L., Washburn, M. P. and Reck-Peterson, S. L. (2017). The Liu, Y., Salter, H. K., Holding, A. N., Johnson, C. M., Stephens, E., Lukavsky, human cytoplasmic dynein interactome reveals novel activators of motility. Elife 6, P. J., Walshaw, J. and Bullock, S. L. (2013). Bicaudal-D uses a parallel, e28257. homodimeric coiled coil with heterotypic registry to coordinate recruitment of Reiner, O., Carrozzo, R., Shen, Y., Wehnert, M., Faustinella, F., Dobyns, W. B., cargos to dynein. Genes Dev. 27, 1233-1246. Caskey, C. T. and Ledbetter, D. H. (1993). Isolation of a Miller–Dicker Loss, O. and Stephenson, F. A. (2015). Localization of the kinesin adaptor proteins lissencephaly gene containing G protein β-subunit-like repeats. Nature 364, trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal 717-721. and cortical neurons. J. Neurosci. Res. 93, 1056-1066. Schlager, M. A., Kapitein, L. C., Grigoriev, I., Burzynski, G. M., Wulf, P. S., Luiro, K., Yliannala, K., Ahtiainen, L., Maunu, H., Järvelä, I., Kyttälä, A. and Keijzer, N., de Graaff, E., Fukuda, M., Shepherd, I. T., Akhmanova, A. et al. Jalanko, A. (2004). Interconnections of CLN3, Hook1 and Rab proteins link (2010). Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D- Batten disease to defects in the endocytic pathway. Hum. Mol. Genet. 13, related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 29, 1637-1651. 3017-3027. Schlager, M. A., Hoang, H. T., Urnavicius, L., Bullock, S. L. and Carter, A. P. MacAskill, A. F., Rinholm, J. E., Twelvetrees, A. E., Arancibia-Carcamo, I. L., (2014a). In vitro reconstitution of a highly processive recombinant human dynein Muir, J., Fransson, A., Aspenstrom, P., Attwell, D. and Kittler, J. T. (2009). complex. EMBO J. 33, 1855-1868. Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Schlager, M. A., Serra-Marques, A., Grigoriev, I., Gumy, L. F., Esteves da Silva, Mitochondria at Synapses. Neuron 61, 541-555. M., Wulf, P. S., Akhmanova, A. and Hoogenraad, C. C. (2014b). Bicaudal d Mach, J. M. and Lehmann, R. (1997). An Egalitarian-BicaudalD complex is family adaptor proteins control the velocity of Dynein-based movements. Cell Rep. essential for oocyte specification and axis determination in Drosophila. Genes 8, 1248-1256. Dev. 11, 423-435. Schroeder, C. M. and Vale, R. D. (2016). Assembly and activation of dynein- Maldonado-Báez, L., Cole, N. B., Krämer, H. and Donaldson, J. G. (2013). dynactin by the cargo adaptor protein Hook3. J. Cell Biol. 214, 309-318. Microtubule-dependent endosomal sorting of clathrin-independent cargo by Schroeder, C. M., Ostrem, J. M., Hertz, N. T. and Vale, R. D. (2014). A Ras-like Hook1. J. Cell Biol. 201, 233-247. domain in the light intermediate chain bridges the dynein motor to a cargo-binding Matanis, T., Akhmanova, A., Wulf, P., Del Nery, E., Weide, T., Stepanova, T., region. Elife 3, e03351.

Galjart, N., Grosveld, F., Goud, B., De Zeeuw, C. I. et al. (2002). Bicaudal-D Schroer, T. A. (2004). Dynactin. Annu. Rev. Cell Dev. Biol. 20, 759-779. Journal of Cell Science

6 CELL SCIENCE AT A GLANCE Journal of Cell Science (2019) 132, jcs227132. doi:10.1242/jcs.227132

Shao, C.-Y., Zhu, J., Xie, Y.-J., Wang, Z., Wang, Y.-N., Wang, Y., Su, L.-D., Zhou, Walenta, J. H., Didier, A. J., Liu, X. and Krämer, H. (2001). The Golgi-associated L., Zhou, T.-H. and Shen, Y. (2013). Distinct functions of nuclear distribution hook3 protein is a member of a novel family of microtubule-binding proteins. J. Cell proteins LIS1, Ndel1 and NudCL in regulating axonal mitochondrial transport. Biol. 152, 923-934. Traffic 14, 785-797. Wang, X. and Schwarz, T. L. (2009). The mechanism of Ca2+-dependent Short, B., Preisinger, C., Schaletzky, J., Kopajtich, R. and Barr, F. A. (2002). The regulation of kinesin-mediated mitochondrial motility. Cell 136, 163-174. Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Wang, S. and Zheng, Y. (2011). Identification of a novel dynein binding domain in Curr. Biol. 12, 1792-1795. nudel essential for spindle pole organization in Xenopus egg extract. J. Biol. Chem Simon, G. C., Schonteich, E., Wu, C. C., Piekny, A., Ekiert, D., Yu, X., Gould, 286, 587-593. G. W., Glotzer, M. and Prekeris, R. (2008). Sequential Cyk-4 binding to ECT2 Wang, S., Wu, D., Quintin, S., Green, R. A., Cheerambathur, D. K., Ochoa, S. D., and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis. Desai, A. and Oegema, K. (2015). NOCA-1 functions with γ-tubulin and in parallel EMBO J. 27, 1791-1803. to Patronin to assemble non-centrosomal microtubule arrays in C. elegans. Sladewski, T. E., Billington, N., Ali, M. Y., Bookwalter, C. S., Lu, H., Elife. 4. Krementsova, E. B., Schroer, T. A. and Trybus, K. M. (2018). Recruitment of Waterman-Storer, C., Karki, S. and Holzbaur, E. (1995). The p150Glued two dyneins to an mRNA-dependent Bicaudal D transport complex. Elife. 7, component of the dynactin complex binds to both microtubules and the actin- e36306. related protein centractin (Arp1). Proc. Natl. Acad. Sci. USA 92, 1634-1638. Song, M., Giza, J., Proenca, C. C., Jing, D., Elliott, M., Dincheva, I., Shmelkov, Weiss, K. R. and Littleton, J. T. (2016). Characterization of axonal transport defects S. V., Kim, J., Schreiner, R., Huang, S.-H. et al. (2015). Slitrk5 Mediates BDNF- in Drosophila Huntingtin mutants. J. Neurogenet 30, 212-221. Dependent TrkB receptor trafficking and signaling. Dev. Cell 33, 690-702. Wharton, R. P. and Struhl, G. (1989). Structure of the Drosophila BicaudalD protein Splinter, D., Razafsky, D. S., Schlager, M. A., Serra-Marques, A., Grigoriev, I., and its role in localizing the the posterior determinant nanos. Cell 59, 881-892. Demmers, J., Keijzer, N., Jiang, K., Poser, I., Hyman, A. A. et al. (2012). Whitmarsh, A. J. (2006). The JIP family of MAPK scaffold proteins. Biochem. Soc. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular Trans. 34, 828-832. structures. Mol. Biol. Cell 23, 4226-4241. Wilson, G. M., Fielding, A. B., Simon, G. C., Yu, X., Andrews, P. D., Hames, R. S., Stehman, S. A., Chen, Y., McKenney, R. J. and Vallee, R. B. (2007). NudE and Frey, A. M., Peden, A. A., Gould, G. W. and Prekeris, R. (2005). The FIP3- NudEL are required for mitotic progression and are involved in dynein recruitment Rab11 protein complex regulates recycling endosome targeting to the cleavage to kinetochores. J. Cell Biol. 178, 583-594. furrow during late cytokinesis. Mol. Biol. Cell 16, 849-860. ́ Stowers, R. S., Megeath, L. J., Gorska-Andrzejak, J., Meinertzhagen, I. A. and Wong, Y. C. and Holzbaur, E. L. F. (2014). The regulation of autophagosome Schwarz, T. L. (2002). Axonal transport of mitochondria to synapses depends on dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, milton, a novel Drosophila protein. Neuron 36, 1063-1077. leading to defective cargo degradation. J. Neurosci. 34, 1293-1305. Suter, B. and Steward, R. (1991). Requirement for phosphorylation and localization Wu, M., T. Wang, E. Loh, W. Hong, and Song, H. (2005). Structural basis for of the Bicaudal-D protein in Drosophila oocyte differentiation. Cell 67, 917-926. recruitment of RILP by small GTPase Rab7. EMBO J. 24, 1491-1501. Swan, A. and Suter, B. (1996). Role of Bicaudal-D in patterning the Drosophila egg Xiang, X., Osmani, A. H., Osmani, S. A., Xin, M. and Morris, N. R. (1995). NudF, a chamber in mid-oogenesis. Development 122, 3577-3586. nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene Swan, A., Nguyen, T. and Suter, B. (1999). Drosophila Lissencephaly-1 functions required for neuronal migration. Mol. Biol. Cell 6, 297-310. with Bic-D and dynein in oocyte determination and nuclear positioning. Nat. Cell Xu, L., Sowa, M. E., Chen, J., Li, X., Gygi, S. P. and Harper, J. W. (2008). An FTS/ Biol. 1, 444-449. Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by Szebenyi, G., Hall, B., Yu, R., Hashim, A. I. and Krämer, H. (2007). Hook2 the homotypic vacuolar protein sorting complex. Mol. Biol. Cell 19, 5059-5071. Localizes to the centrosome, binds directly to centriolin/CEP110 and contributes Yamada, M., Toba, S., Yoshida, Y., Haratani, K., Mori, D., Yano, Y., Mimori- to centrosomal function. Traffic 8, 32-46. Kiyosue, Y., Nakamura, T., Itoh, K., Fushiki, S. et al. (2008). LIS1 and NDEL1 Takahide, Kon, Nishiura, M., Ohkura, R. and Toyoshima, Y. Y. and Sutoh, K. coordinate the plus-end-directed transport of cytoplasmic dynein. EMBO J. 27, (2004). Distinct functions of nucleotide-binding/hydrolysis sites in the four AAA 2471-2483. modules of cytoplasmic dynein. Biochemistry 43, 11266-11274. Yang, G.-Z., Yang, M., Lim, Y., Lu, J.-J., Wang, T.-H., Qi, J.-G., Zhong, J.-H. and Tarricone, C., Perrina, F., Monzani, S., Massimiliano, L., Kim, M.-H., Zhou, X.-F. (2012). Huntingtin associated protein 1 regulates trafficking of the Derewenda, Z. S., Knapp, S., Tsai, L.-H. and Musacchio, A. (2004). Coupling amyloid precursor protein and modulates amyloid beta levels in neurons. PAF signaling to dynein regulation: structure of LIS1 in complex with PAF- acetylhydrolase. Neuron 44, 809-821. J. Neurochem. 122, 1010-1022. Terawaki, S., Yoshikane, A., Higuchi, Y. and Wakamatsu, K. (2015). Structural Yasuda, J., Whitmarsh, A. J., Cavanagh, J., Sharma, M. and Davis, R. J. (1999). basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil The JIP group of mitogen-activated protein kinase scaffold proteins. Mol. Cell. with homotypic registry. Biochem. Biophys. Res. Commun. 460, 451-456. Biol. 19, 7245-7254. Torisawa, T., Ichikawa, M., Furuta, A., Saito, K., Oiwa, K., Kojima, H., Yazaki, Y., Hara, Y., Tamaki, H., Fukaya, M. and Sakagami, H. (2014). Endosomal Toyoshima, Y. Y. and Furuta, K. (2014). Autoinhibition and cooperative localization of FIP3/Arfophilin-1 and its involvement in dendritic formation of activation mechanisms of cytoplasmic dynein. Nat. Cell Biol. 16, 1118-1124. mouse hippocampal neurons. Brain Res. 1557, 55-65. Toropova, K., Zou, S., Roberts, A. J., Redwine, W. B., Goodman, B. S., Reck- Yeh, T.-Y., Quintyne, N. J., Scipioni, B. R., Eckley, D. M. and Schroer, T. A. ’ Peterson, S. L. and Leschziner, A. E. (2014). Lis1 regulates dynein by sterically (2012). Dynactin s pointed-end complex is a cargo-targeting module. Mol. Biol. blocking its mechanochemical cycle. Elife. 3, e03372. Cell 23, 3827-3837. Tsai, J.-W., Bremner, K. H. and Vallee, R. B. (2007). Dual subcellular roles for LIS1 Yi, J. Y., Ori-McKenney, K. M., McKenney, R. J., Vershinin, M., Gross, S. P. and and dynein in radial neuronal migration in live brain tissue. Nat. Neurosci. 10, Vallee, R. B. (2011). High-resolution imaging reveals indirect coordination of 970-979. opposite motors and a role for LIS1 in high-load axonal transport. J. Cell Biol. 195, Twelvetrees, A. E., Yuen, E. Y., Arancibia-Carcamo, I. L., MacAskill, A. F., 193-201. Rostaing, P., Lumb, M. J., Humbert, S., Triller, A., Saudou, F., Yan, Z. et al. Zhang, J., Zhuang, L., Lee, Y., Abenza, J. F., Peñalva, M. A. and Xiang, X. (2010). (2010). Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and The microtubule plus-end localization of Aspergillus dynein is important for Disrupted by Mutant Huntingtin. Neuron 65, 53-65. dynein-early-endosome interaction but not for dynein ATPase activation. J. Cell Urnavicius, L., K. Zhang, A. G. Diamant, C. Motz, M. A. Schlager, M. Yu, N. A. Sci. 123, 3596-3604. Patel, C. V. Robinson and Carter, A. P. (2015). The structure of the dynactin Zhang, K., Foster, H. E., Rondelet, A., Lacey, S. E., Bahi-Buisson, N., Bird, A. W. complex and its interaction with dynein. Science 347, 1441-1446. and Carter, A. P. (2017). Cryo-EM Reveals How Human Cytoplasmic Dynein Is Urnavicius, L., Lau, C. K., Elshenawy, M. M., Morales-Rios, E., Motz, C., Yildiz, Auto-inhibited and Activated. Cell 169, 1303-1314.e18. A. and Carter, A. P. (2018). Cryo-EM shows how dynactin recruits two dyneins for Zhang, J., Yao, X., Fischer, L., Abenza, J. F., Penalva,̃ M. A. and Xiang, X. (2011). faster movement. Nature 554, 202-206. The p25 subunit of the dynactin complex is required for dynein-early endosome van Spronsen, M., Mikhaylova, M., Lipka, J., Schlager, M. A., van den Heuvel, interaction. J. Cell Biol. 193, 1245-1255. D. J., Kuijpers, M., Wulf, P. S., Keijzer, N., Demmers, J., Kapitein, L. C. et al. Zhang, J., Qiu, R., Arst, H. N., Peñalva, M. A. and Xiang, X. (2014). HookA is a (2013). TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to novel dynein-early endosome linker critical for cargo movement in vivo. J. Cell axons and dendrites. Neuron 77, 485-502. Biol. 204, 1009-1026. Verhey, K. J., Meyer, D., Deehan, R., Blenis, J., Schnapp, B. J., Rapoport, T. A. Zyłkiewicz, E., Kijańska, M., Choi, W.-C., Derewenda, U., Derewenda, Z. S. and and Margolis, B. (2001). Cargo of kinesin identified as JIP scaffolding proteins Stukenberg, P. T. (2011). The N-terminal coiled-coil of Ndel1 is a regulated and associated signaling molecules. J. Cell Biol. 152, 959-970. scaffold that recruits LIS1 to dynein. J. Cell Biol. 192, 433-445. Journal of Cell Science