Abstract
Kinesin superfamily proteins (KIFs) are microtubule-dependent molecular motors that serve as sources of force for intracellular transport and cell division. Recent studies have revealed new roles of KIFs as microtubule stabilizers and depolymerizers, and these activities are fundamental to cellular morphogenesis and mammalian development. KIF2A and KIF19A have microtubule-depolymerizing activities and regulate the neuronal morphology and cilia length, respectively. KIF21A and KIF26A work as microtubule stabilizers that regulate axonal morphology. Morphological defects that are similar to human diseases are observed in mice in which these KIF genes have been deleted. Actually, KIF2A and KIF21A have been identified as causes of human neuronal diseases. In this review, the functions of these atypical KIFs that regulate microtubule dynamics are discussed. Moreover, some interesting unanswered questions and hypothetical answers to them are discussed.
Similar content being viewed by others
References
Aizawa H, Sekine Y, Takemura R, Zhang Z, Nangaku M, Hirokawa N (1992) Kinesin family in murine central nervous system. J Cell Biol 119:1287–1296
Alberts B (2008) Molecular biology of the cell. Garland Science, New York
Andrews PD, Ovechkina Y, Morrice N et al (2004) Aurora B regulates MCAK at the mitotic centromere. Dev Cell 6:253–268
Bieling P, Telley IA, Surrey T (2010) A minimal midzone protein module controls formation and length of antiparallel microtubule overlaps. Cell 142:420–432
Bringmann H, Skiniotis G, Spilker A, Kandels-Lewis S, Vernos I, Surrey T (2004) A kinesin-like motor inhibits microtubule dynamic instability. Science 303:1519–1522
Chan KY, Ersfeld K (2010) The role of the Kinesin-13 family protein TbKif13-2 in flagellar length control of Trypanosoma brucei. Mol Biochem Parasitol 174:137–140
Cheng L, Desai J, Miranda CJ et al (2014) Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling. Neuron 82:334–349
Cleveland DW, Hwo SY, Kirschner MW (1977) Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol 116:207–225
Cole DG, Chinn SW, Wedaman KP, Hall K, Vuong T, Scholey JM (1993) Novel heterotrimeric kinesin-related protein purified from sea urchin eggs. Nature 366:268–270
Cole DG, Diener DR, Himelblau AL, Beech PL, Fuster JC, Rosenbaum JL (1998) Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J Cell Biol 141:993–1008
Cross RA, McAinsh A (2014) Prime movers: the mechanochemistry of mitotic kinesins. Nat Rev Mol Cell Biol 15:257–271
Desai A, Verma S, Mitchison TJ, Walczak CE (1999) Kin I kinesins are microtubule-destabilizing enzymes. Cell 96:69–78
Endow SA, Henikoff S, Soler-Niedziela L (1990) Mediation of meiotic and early mitotic chromosome segregation in Drosophila by a protein related to kinesin. Nature 345:81–83
Ghosh-Roy A, Goncharov A, Jin Y, Chisholm AD (2012) Kinesin-13 and tubulin posttranslational modifications regulate microtubule growth in axon regeneration. Dev Cell 23:716–728
Hall DH, Hedgecock EM (1991) Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 65:837–847
Harada A, Oguchi K, Okabe S et al (1994) Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 369:488–491
Harada A, Teng J, Takei Y, Oguchi K, Hirokawa N (2002) MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction. J Cell Biol 158:541–549
He M, Subramanian R, Bangs F et al (2014) The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat Cell Biol 16:663–672
Heanue TA, Pachnis V (2007) Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci 8:466–479
Hirokawa N, Noda Y, Tanaka Y, Niwa S (2009) Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10:682–696
Hirokawa N, Niwa S, Tanaka Y (2010) Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 68:610–638
Homma N, Takei Y, Tanaka Y et al (2003) Kinesin superfamily protein 2A (KIF2A) functions in suppression of collateral branch extension. Cell 114:229–239
Ishikawa H, Marshall WF (2011) Ciliogenesis: building the cell’s antenna. Nat Rev Mol Cell Biol 12:222–234
Izant JG, McIntosh JR (1980) Microtubule-associated proteins: a monoclonal antibody to MAP2 binds to differentiated neurons. Proc Natl Acad Sci USA 77:4741–4745
Jiang K, Wang J, Liu J et al (2009) TIP150 interacts with and targets MCAK at the microtubule plus ends. EMBO Rep 10:857–865
Kamiya R (2002) Functional diversity of axonemal dyneins as studied in Chlamydomonas mutants. Int Rev Cytol 219:115–155
Kanai Y, Takemura R, Oshima T et al (1989) Expression of multiple tau isoforms and microtubule bundle formation in fibroblasts transfected with a single tau cDNA. J Cell Biol 109:1173–1184
Kim H, Binder LI, Rosenbaum JL (1979) The periodic association of MAP2 with brain microtubules in vitro. J Cell Biol 80:266–276
Kozminski KG, Beech PL, Rosenbaum JL (1995) The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated with the flagellar membrane. J Cell Biol 131:1517–1527
Lee T, Langford KJ, Askham JM, Brüning-Richardson A, Morrison EE (2008) MCAK associates with EB1. Oncogene 27:2494–2500
Maeder CI, Shen K, Hoogenraad CC (2014) Axon and dendritic trafficking. Curr Opin Neurobiol 27C:165–170
Marszalek JR, Weiner JA, Farlow SJ, Chun J, Goldstein LS (1999) Novel dendritic kinesin sorting identified by different process targeting of two related kinesins: KIF21A and KIF21B. J Cell Biol 145:469–479
Miki H, Setou M, Kaneshiro K, Hirokawa N (2001) All kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci USA 98:7004–7011
Niwa S, Nakajima K, Miki H, Minato Y, Wang D, Hirokawa N (2012) KIF19A is a microtubule-depolymerizing kinesin for ciliary length control. Dev Cell 23:1167–1175
Noda Y, Sato-Yoshitake R, Kondo S, Nangaku M, Hirokawa N (1995) KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by kinesin heavy chain or KIF3A/B. J Cell Biol 129:157–167
Noda Y, Niwa S, Homma N, Fukuda H, Imajo-Ohmi S, Hirokawa N (2012) Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches. Proc Natl Acad Sci USA 109:1725–1730
Ogawa T, Nitta R, Okada Y, Hirokawa N (2004) A common mechanism for microtubule destabilizers—M type kinesins stabilize curling of the protofilament using the class-specific neck and loops. Cell 116:591–602
Otsuka AJ, Jeyaprakash A, García-Añoveros J et al (1991) The C. elegans unc-104 gene encodes a putative kinesin heavy chain-like protein. Neuron 6:113–122
Piao T, Luo M, Wang L et al (2009) A microtubule depolymerizing kinesin functions during both flagellar disassembly and flagellar assembly in Chlamydomonas. Proc Natl Acad Sci USA 106:4713–4718
Poirier K, Lebrun N, Broix L et al (2013) Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat Genet 45:639–647
Rosenbaum JL, Witman GB (2002) Intraflagellar transport. Nat Rev Mol Cell Biol 3:813–825
Schlaitz AL, Srayko M, Dammermann A et al (2007) The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes and regulates mitotic spindle assembly. Cell 128:115–127
Scholey JM, Porter ME, Grissom PM, McIntosh JR (1985) Identification of kinesin in sea urchin eggs, and evidence for its localization in the mitotic spindle. Nature 318:483–486
Srayko M, Kaya A, Stamford J, Hyman AA (2005) Identification and characterization of factors required for microtubule growth and nucleation in the early C. elegans embryo. Dev Cell 9:223–236
Takei Y, Teng J, Harada A, Hirokawa N (2000) Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J Cell Biol 150:989–1000
Teng J, Takei Y, Harada A, Nakata T, Chen J, Hirokawa N (2001) Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization. J Cell Biol 155:65–76
Vale RD, Reese TS, Sheetz MP (1985) Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 42:39–50
van der Vaart B, van Riel WE, Doodhi H et al (2013) CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor. Dev Cell 27:145–160
Verhey KJ, Hammond JW (2009) Traffic control: regulation of kinesin motors. Nat Rev Mol Cell Biol 10:765–777
Walczak CE, Mitchison TJ, Desai A (1996) XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 84:37–47
Walczak CE, Gayek S, Ohi R (2013) Microtubule-depolymerizing kinesins. Annu Rev Cell Dev Biol 29:417–441
Weisenberg RC (1972) Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177:1104–1105
Wordeman L, Mitchison TJ (1995) Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol 128:95–104
Yamada K, Andrews C, Chan WM et al (2003) Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nat Genet 35:318–321
Yamazaki H, Nakata T, Okada Y, Hirokawa N (1996) Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. Proc Natl Acad Sci USA 93:8443–8448
Zhou R, Niwa S, Homma N, Takei Y, Hirokawa N (2009) KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development. Cell 139:802–813
Acknowledgements
I deeply thank Dr. Nobutaka Hirokawa (University of Tokyo) for his assistance and mentorship. This work is supported by the Naito Foundation, the Kanae Foundation for the Promotion of Medical Science, and a JSPS postdoctoral fellowship for research abroad.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Niwa, S. Kinesin superfamily proteins and the regulation of microtubule dynamics in morphogenesis. Anat Sci Int 90, 1–6 (2015). https://doi.org/10.1007/s12565-014-0259-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12565-014-0259-5