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The Dynein Family at a Glance Peter Höök and Richard B

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The Dynein Family at a Glance Peter Höök and Richard B Cell Science at a Glance 4369 The dynein family at a functions. Although at least 14 classes of accessory subunits bind; and a ~380 kDa kinesin and 17 classes of myosin have motor domain. The motor domain glance been identified, the dyneins fall into contains six discernible AAA ATPase Peter Höök* and Richard B. only two major classes, axonemal and units, identifying the dynein HC as a Vallee cytoplasmic dyneins, based on both divergent member of the AAA+ family functional and structural criteria. of ATPases (Neuwald et al., 1999). Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Axonemal dyneins are responsible for Members of the AAA+ family are *Author for correspondence (e-mail: ciliary and flagellar beating; cytoplasmic involved in a very wide range of [email protected]) dyneins are involved in intracellular functions but have a common feature: the Journal of Cell Science 119, 4369-4371 transport, mitosis, cell polarization and formation of ring-shaped oligomeric Published by The Company of Biologists 2006 directed cell movement complexes of the AAA ATPase module. doi:10.1242/jcs.03176 Within the AAA+ proteins, dynein All dynein forms that have occupies a divergent branch along with Three families of cytoskeletal motor been identified biochemically are midasin (Iyer et al., 2004). This branch protein – the myosins, kinesins and multisubunit proteins. Each has one to is characterized by the incorporation of dyneins – have evolved to mediate three heavy chains (HCs) of >500 kDa; all six AAA modules within a single transport of cells and of structures and these correspond to the number of giant polypeptide. The AAA family has materials within cells in eukaryotes. morphologically identifiable heads and members in prokaryotes and it seems Whereas myosin uses actin polymers to contain the motor domains of the likely, therefore, that the dyneins had carry out its tasks, kinesin and dynein are molecule. The dynein HC forms two their origin very early in evolution. microtubule-associated motors. Dyneins prominent structures: a ~160 kDa N- In dynein, energy from nucleotide use energy from ATP hydrolysis to terminal domain that forms the base of hydrolysis at the AAA units is conveyed power a wide variety of cellular the molecule, to which most of the to the base of the molecule and to the The Dynein Family at a Glance Peter Höök and Richard B. Vallee + S. pombe D. discoideum C. elegans - D. melanogaster D. rerio H. sapiens R. norvegicus M. musculus U. maydis Journal of Cell Science E. nidulans + + A. fumigatus Dynein 1 I A. oryzae - + - + N. crassa - - N. haematococca - - + - + P. tetraurelia T. thermophila Cytoplasmic + C. albicans E. gossypii S. cerevisiae G. lamblia D. melanogaster L. mexicana T. thermophila C. elegans Dynein 2 II T. gratilla Microtubule Axoneme R. norvegicus M. musculus Dynein 1 Inner-arm dynein C. reinhardtii Outer-arm dynein III Dynein 2 Outer-arm dynein D. melanogaster D. melanogaster H. sapiens DHC9 Clamp loader A. crassispina DnaA/Cdc6/ORC T. gratilla H. sapiens DHC11 Outer-arm dynein IV Classical M. musculus DHC11 AAA D. melanogaster AAA+ D. hydei DHC7 l HsIU/ClpX/Lon/Clp C. reinhardtii jcs.biologists.org Dynein T. thermophila Helix 2 C. reinhardtii insert M. musculus DHC5 Axonema Midasin H. sapiens DHC5 Outer-arm dynein V M. musculus DHC8 H. sapiens DHC8 D. melanogaster Inner-arm dynein C. reinhardtii DHC1 VI Stem/tail Linker AAA1 AAA2 AAA3 AAA4Stalk AAA5 AAA6 CT D. melanogaster C. reinhardtii DHC10 Inner-arm dynein H. sapiens DHC7 VII ... ... ..................................... .......... .... ... ....... ........ ... H. sapiens DHC3 LIC C. reinhardtii DHC9 IC HC Conserved residues © Journal of Cell Science 2006 (119, pp. 4369-4371) (See poster insert) 4370 Journal of Cell Science 119 (21) microtubule-binding stalk for force arm dyneins are two- and one-headed and below), it coexists with axonemal production (Burgess et al., 2003). The arrayed in a repeating pattern along the A- dyneins in cilia and flagella. stalk is predicted to consist of a 15-nm- microtubule. Each of the flagellar dyneins long antiparallel coiled-coil ␣-helix interacts with the B microtubule of the crowned with a globular structure for adjacent outer doublet. Seven subtypes of Evolutionary relationship among microtubule association (Gee et al., Chlamydomonas axonemal inner-arm dyneins 1997). dynein have been identified (Kagami and The diverse forms of kinesin and myosin Kamiya, 1992); one forms a HC have been judged to comprise clear A diversity of accessory subunits, heterodimer; the rest are monomeric, one- subfamilies. The definition of the referred to as intermediate, light headed structures. subcategories has been made on the basis intermediate and light chains are also of phylogenetic analysis of the motor found associated with the dyneins. Most, subunits (HCs), but also on the but not all, of these subunits are Cytoplasmic dyneins composition and organization of the associated with the cargo-binding base Two forms of cytoplasmic dynein have nonmotor domains, which are highly of the dynein molecule. Dynein-isoform- been identified: cytoplasmic dynein 1 distinctive between subfamilies. specific intermediate chains are found in and cytoplasmic dynein 2. Both Differences in physiological and some axonemal dyneins as well as in assemble as homodimers, but their mechanochemical properties have cytoplasmic dynein 1. Some light chains distributions and functions within the correlated well with family boundaries. are shared between axonemal dyneins, cell differ markedly. Cytoplasmic dynein By contrast, the organization of both the cytoplasmic dynein 1 and other proteins. 1 is far more abundant and is found motor and nonmotor portion of the Isoform-specific light intermediate in all microtubule-containing cells. It dynein HCs is remarkably well chains are associated with both associates with and transports elements conserved. Differences in physiological cytoplasmic dyneins but not with of the Golgi apparatus, lysosomes, and function and subcellular localization axonemal dyneins. late and recycling endosomes, and is have provided the clearest indication of responsible for retrograde axonal boundaries. Some differences in domain transport. It also associates with diverse organization have been discerned Axonemal dyneins protein and RNA-containing complexes, between dyneins, but these are very The axoneme is a highly specialized and which it transports or maintains at limited in scope. For example, the C- highly conserved, array of microtubules. microtubule minus ends. Cytoplasmic terminal (CT) region of the motor Motile axonemes in flagella and many dynein 1 also associates with domain is found in some, but not all, forms of cilia almost universally consist kinetochores, where it has been dynein HCs, although the functional of 20 microtubules, of which two are implicated in microtubule capture and significance of this region is centrally located and nine are fused pairs the removal of checkpoint proteins to incompletely understood (Vallee and (the outer doublet) forming a surrounding permit entry into anaphase. This form of Höök, 2006). Isoforms of the Journal of Cell Science cylinder. Dyneins connect the outer cytoplasmic dynein also associates with intermediate chain (IC) family bind to doublets and force them to slide against the cell cortex during division and during some axonemal dyneins and cytoplasmic each other (Summers and Gibbons, 1971). directed migration, as well as residing at dynein 1 but not cytoplasmic dynein 2. Most ultrastructural and genetic evidence other sites. These latter roles have The full range of IC-binding axonemal for subspecialization of the axonemal suggested an additional feature of dynein dynein forms remains to be explored. dyneins has been obtained in studies function: it may serve not only in The light chains (LCs), which bind of the biflagellate green alga transport motor, but also in producing to dynein almost exclusively through Chlamydomonas reinhardtii and the tension along or at the ends of the ICs as scaffolds, are found in ciliate protozoan Tetrahymena pyriformis. microtubules from fixed cellular sites. cytoplasmic dynein 1 and some, but not Sea urchin sperm flagella have also been all, axonemal dyneins, as well as non- used for biochemical analysis of By contrast, cytoplasmic dynein 2 is dynein proteins. The LCs, therefore, like axonemal dyneins, but limited work has found almost exclusively within and the ICs, have not been of significant been performed in vertebrates. At least around the base of cilia and flagella, value in distinguishing dynein five biochemically defined forms of where it is engaged in retrograde subfamilies. The LICs, however, are dynein (and even more gene products) can intraflagellar transport (Porter et al., associated with cytoplasmic dynein 1 be found in a given type of cilium or 1999; Pazour et al., 1999; Mikami et al., and dynein 2, but, so far, with no known flagellum, but correlating dynein genes 2002). This form of motility is required axonemal dyneins. These subunits, with specific dynein structures in the for axonemal maintenance. In addition, therefore, serve as a further means to axoneme has been a long and challenging cytoplasmic dynein 2 is responsible for distinguish the two major dynein process. All axonemal dyneins are stably transport through modified ciliary subfamilies. Their binding site within associated with the complete microtubule structures, such as the connecting cilium their respective dynein HCs is also (the A microtubule)
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