Erratum Kinesins at a glance Sharyn A. Endow, F. Jon Kull and Honglei Liu Journal of Cell Science 123, 4000 © 2010. Published by The Company of Biologists Ltd doi:10.1242/jcs.082667doi:10. There was an error published in J. Cell Sci. 123, 3420-3423. We misprinted the sentence in the acknowledgements that states the American Heart Association (AHA) as the funding body supporting F. Jon Kull. The correct sentence is given below: The authors’ research on kinesins is supported by NIH GM046225 and March of Dimes 1-FY07-443 Grants to S.A.E., and AHA Scientist Development Grant 0330345N to F.J.K. We apologise for this mistake. 3420 Cell Science at a Glance Kinesins at a glance Kinesin was discovered in 1985 – 25 years ago – into the public databases (Yang et al., 1989). The based on its motility in cytoplasm extruded predicted KHC protein contained a motor Sharyn A. Endow1,*, F. Jon Kull2 from the giant axon of the squid (Allen et al., domain with ATP- and microtubule-binding and Honglei Liu1 1982; Brady et al., 1982; Vale et al., 1985). The sites, an -helical coiled-coil dimerization 1Department of Cell Biology, Duke University Medical purified protein, now known as kinesin-1, domain (also referred to as the stalk), and a tail Center, Durham, NC 27710, USA consisted of two heavy chains with motor that can interact with vesicles or organelles 2 Department of Chemistry, Dartmouth College, New activity that were associated with two light through light chains. A large number of kinesin- Hanover, NH 03755, USA *Author for correspondence ([email protected]) chains, which mediate motor binding to vesicles related proteins were identified in rapid and other cargo. Vesicle movement was distal to succession by sequence homology to Drosophila Journal of Cell Science 123, 3420-3424 © 2010. Published by The Company of Biologists Ltd the cell body, towards microtubule plus ends, KHC. They included the first kinesin-14 doi:10.1242/jcs.064113 consistent with the proposal that the motor was proteins, which, despite their sequence the basis of fast axonal transport (Allen et al., homology to kinesin-1, were subsequently This article is part of a Minifocus on microtubule 1982; Brady et al., 1982). demonstrated to be minus-end motors. Screens dynamics. For further reading, please see related For several years, kinesin-1 was the only for kinesins, on the basis of conserved protein articles: ‘Microtubule plus-end tracking proteins motor protein known that moved on motifs, revealed a large number of kinesin- (+TIPs)’ by Anna Akhmanova and Michel O. Steinmetz (J. Cell Sci. 123, 3415-3419), ‘Tubulin microtubules towards their plus ends, the related proteins in a given organism – as many as depolymerization may be an ancient biological motor opposite direction the previously discovered ~50 in human – each containing a highly process’ by J. Richard McIntosh et al. (J. Cell Sci. 123, 3425-3434), ‘Towards a quantitative understanding of axonemal dyneins move. Strikingly, many conserved motor domain that identified the mitotic spindle assembly and mechanics’ by Alex kinesin-related proteins were reported in the protein as a kinesin family member. Mogilner and Erin Craig (J. Cell Sci. 123, 3435-3445) early 1990s, soon after the first sequence of a Phylogenetic analysis defined groups within and ‘Post-translational modifications of microtubules’ by Dorota Wloga and Jacek Gaertig (J. Cell Sci. 123, gene encoding a kinesin-1 heavy chain, the kinesin family that perform similar cellular pp. 3447-3455). Drosophila melanogaster Khc, was deposited functions in different cells or organisms (Kim Journal of Cell Science (See poster insert) Journal of Cell Science 123 (20) 3421 and Endow, 2000). A standardized system of microtubules. Kinesin-5, a homotetrameric side, a design conserved in the myosins (Kull et kinesin nomenclature was introduced in 2004, motor, contains a stalk formed by interactions al., 1996; Sablin et al., 1996). The nucleotide- renaming the groups by number (Lawrence et between the coiled coils of two anti-parallel binding cleft on one side of the central -sheet al., 2004). There are currently 14 groups and dimers (Tao et al., 2006); the motor can bind by contains a highly conserved GQTGSGKT many ungrouped or orphan kinesins. Among its heads to different microtubules to crosslink motif that forms the P-loop. The microtubule- these, three kinesins – kinesin-1, kinesin-14 and and slide microtubules in mitosis. binding site on the opposite side includes the kinesin-13 – highlight the diverse structure and Other kinesins dimerize dynamically by structural elements L11-4-L12-5, which function of the family. coiled-coil stalk formation, thereby regulating interact with tubulin and undergo movement motor activity. C. elegans kinesin-3 Unc104 between the ADP and ATP states. The motor Kinesin diversity exists as a monomer, but, remarkably, forms contains highly conserved switch I (SSRSH) Kinesin-1, the first-discovered kinesin, has been dimers with velocities much faster than kinesin- and II (DLAGSE) motifs, which change in studied extensively. The development of single- 1 (Tomishige et al., 2002). The monomer neck – conformation during the ATP hydrolysis cycle, molecule assays and the early finding that single the region of the stalk adjacent to the head – can similar to their counterparts in G-proteins kinesin-1 molecules move processively along inhibit dimerizaton by folding back onto itself (Rice et al., 1999; Yun et al., 2001; Hirose et microtubules (Howard et al., 1989) made it (Al-Bassam et al., 2003). Unc104 binds to lipid al., 2006). Switch I and II form a salt-bridge possible to measure the steps and force produced membranes and can dimerize when clustered in that, in myosin, closes the nucleotide-binding by single motors. Mutant analysis showed that rafts (Klopfenstein et al., 2002). cleft, enabling the motor to hydrolyze ATP kinesin-1 has an essential role in vesicle Some kinesins associate with different (Geeves and Holmes, 1999). The closed transport in neuronal cells (Saxton et al., 1991). proteins through a coiled-coil stalk. For conformation has now been seen in a crystal Homologs have been found in a wide range of example, two different kinesin proteins dimerize structure of frog kinesin-5 Eg5 bound to AMP- organisms: from yeast, Caenorhabditis elegans and associate with a non-motor protein to form PNP (a nonhydrolyzable ATP analog) (Parke et and Drosophila, to the mouse and human. hetereotrimeric kinesin-2 (Cole et al., 1993); al., 2010). Two other kinesins – Ncd, a Drosophila budding yeast kinesin-14 Kar3, however, can The motor domain is structurally conserved kinesin-14, and MCAK, a Chinese hamster dimerize either with itself or with two non- among the kinesin proteins; differences in kinesin-13 – have been widely studied because motor proteins, Vik1 and Cik1 (Manning et al., motility and cellular function are largely due to of their distinct motor properties. Ncd was the 1999; Barrett et al., 2000). Dimerization with regions outside the catalytic core. Motor first minus-end kinesin motor reported (Walker Cik1 alters Kar3 structurally and converts it into directionality is determined by the region et al., 1990; McDonald et al., 1990) and has a faster motor (Chu et al., 2005). Strikingly, the adjacent to the motor core, the kinesin-1 neck provided crucial information regarding motor Vik1 C-terminal globular domain contains a linker or Ncd neck (Endow, 1999). The directionality and the mechanism of kinesin fold similar to the kinesin catalytic core, kinesin-1 neck linker connects the head to function. MCAK was identified in an antibody although it lacks an ATP-binding cleft the stalk (Kozielski et al., 1997) and has been screen for kinesins and shown to be a (Allingham et al., 2007). proposed to dock onto the motor core in the ATP centromere-associated protein (Wordeman and The tail binds to cellular cargo and is state and undock after hydrolysis, producing Mitchison, 1995). Subsequent studies resulted important for transport, but has been less well force to drive motor movement along Journal of Cell Science in the provocative finding that the motor is studied than the head and stalk. Kinesin-1 microtubules (Rice et al., 1999). Although neck targeted to microtubule ends where it removes binding to vesicles and organelles can occur linker docking has been observed in crystal tubulin dimers, destabilizing microtubules and through light chains that exist in different structures, its role in generating force has been regulating microtubule dynamics (Desai et al., isoforms and arise by alternative splicing (Cyr controversial because it occurs with a small free 1999; Wordeman, 2010; Ems-McClung and et al., 1991), although adaptor or scaffold energy change (Rice et al., 2003). Recently, the Walczak, 2010). proteins have now been identified that bind ‘cover strand’, a structural element at the N- kinesins to cargo (Hirokawa et al., 2009). For terminus of the motor, has been proposed to Kinesin structural organization and example, the adaptor protein Milton mediates dock onto the catalytic domain together with the regulation kinesin-1 binding to mitochondria, which is neck linker to drive kinesin-1 steps along All kinesins contain a motor domain – the head – inhibited by Ca2+. Further molecules are being microtubules (Hwang et al., 2008). This usually attached to a stalk and tail, but the discovered that facilitate kinesin-1 binding to hypothesis is supported by mutant analysis position of the head varies – it is at the N- endosomes, vesicles and organelles (Hirokawa showing that the cover strand is essential for terminus of kinesin-1, C-terminus of kinesin-14 et al., 2009). Other kinesins, such as kinesin-14 kinesin-1 motility (Khalil et al., 2008). and centrally located in kinesin-13 (Kim and Ncd, bind to microtubules by their tails, as well Ncd and other kinesin-14 motors lack a neck Endow, 2000).