Forty-five genes that encode kinesin superfamily proteins (also known as KIFs) have been discovered in the mouse and human genomes.
KIFs are molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs, along the microtubule system.
The mechanisms by which different kinesins recognize, bind and unload specific cargo have been identified.
The spatiotemporal delivery of cargos by KIF-based transport can be regulated by phosphorylation, G proteins and Ca2+ levels.
It is now recognized that kinesins have unexpected roles in the regulation of physiological processes, such as higher brain function, tumour suppression and developmental patterning.
Intracellular transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified. Furthermore, recent molecular genetic experiments have uncovered important and unexpected roles for kinesins in the regulation of such physiological processes as higher brain function, tumour suppression and developmental patterning. These findings open exciting new areas of kinesin research.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519–526 (1998).
Hirokawa, N. & Noda, Y. Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics. Physiol. Rev. 88, 1089–1118 (2008).
Hirokawa, N. & Takemura, R. Molecular motors and mechanisms of directional transport in neurons. Nature Rev. Neurosci. 6, 201–214 (2005).
Vale, R. D. The molecular motor toolbox for intracellular transport. Cell 112, 467–480 (2003).
Hirokawa, N. Cross-linker system between neurofilaments, microtubules, and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method. J. Cell Biol. 94, 129–142 (1982). A pioneering paper that describes structural candidates of microtubule-based motor proteins in the axon.
Aizawa, H. et al. Kinesin family in murine central nervous system. J. Cell Biol. 119, 1287–1296 (1992). The first identification of kinesin superfamily proteins using molecular biology techniques.
Miki, H., Setou, M., Kaneshiro, K. & Hirokawa, N. All kinesin superfamily protein, KIF, genes in mouse and human. Proc. Natl Acad. Sci. USA 98, 7004–7011 (2001).
Lawrence, C. J. et al. A standardized kinesin nomenclature. J. Cell Biol. 167, 19–22 (2004).
Dagenbach, E. M. & Endow, S. A. A new kinesin tree. J. Cell Sci. 117, 3–7 (2004).
Terada, S. Where does slow axonal transport go? Neurosci. Res. 47, 367–372 (2003).
Hall, D. H. & Hedgecock, E. M. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 65, 837–847 (1991).
Okada, Y., Yamazaki, H., Sekine-Aizawa, Y. & Hirokawa, N. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell 81, 769–780 (1995).
Zhao, C. et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1B β. Cell 105, 587–597 (2001). A Kif1b heterozygote mouse was generated by gene targeting and found to be a good model of progressive peripheral neuropathies.
Vale, R. D., Reese, T. S. & Sheetz, M. P. Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 42, 39–50 (1985). Identifies conventional kinesin (kinesin 1).
Hirokawa, N. et al. Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration. Cell 56, 867–878 (1989). Demonstrates the structure of kinesins using electron microscopy and reveals that kinesins are built from heavy chains and light chains.
Yang, J. T., Laymon, R. A. & Goldstein, L. S. A three-domain structure of kinesin heavy chain revealed by DNA sequence and microtubule binding analyses. Cell 56, 879–889 (1989).
Kanai, Y. et al. KIF5C, a novel neuronal kinesin enriched in motor neurons. J. Neurosci. 20, 6374–6384 (2000).
Gyoeva, F. K., Sarkisov, D. V., Khodjakov, A. L. & Minin, A. A. The tetrameric molecule of conventional kinesin contains identical light chains. Biochemistry 43, 13525–13531 (2004).
Byrd, D. T. et al. UNC-16, a JNK-signaling scaffold protein, regulates vesicle transport in C. elegans. Neuron 32, 787–800 (2001).
Toda, H. et al. UNC-51/ATG1 kinase regulates axonal transport by mediating motor-cargo assembly. Genes Dev. 22, 3292–3307 (2008).
Diefenbach, R. J., Diefenbach, E., Douglas, M. W. & Cunningham, A. L. The heavy chain of conventional kinesin interacts with the SNARE proteins SNAP25 and SNAP23. Biochemistry 41, 14906–14915 (2002).
Su, Q., Cai, Q., Gerwin, C., Smith, C. L. & Sheng, Z. H. Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons. Nature Cell Biol. 6, 941–953 (2004).
Nangaku, M. et al. KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79, 1209–1220 (1994).
Wozniak, M. J., Melzer, M., Dorner, C., Haring, H. U. & Lammers, R. The novel protein KBP regulates mitochondria localization by interaction with a kinesin-like protein. BMC Cell Biol. 6, 35 (2005).
Tanaka, Y. et al. Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93, 1147–1158 (1998).
Cai, Q., Gerwin, C. & Sheng, Z. H. Syntabulin-mediated anterograde transport of mitochondria along neuronal processes. J. Cell Biol. 170, 959–969 (2005).
Glater, E. E., Megeath, L. J., Stowers, R. S. & Schwarz, T. L. Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J. Cell Biol. 173, 545–557 (2006).
Cho, K. I. et al. Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function. Traffic 8, 1722–1735 (2007).
Wang, X. & Schwarz, T. L. The mechanism of Ca2+-dependent regulation of kinesin-mediated mitochondrial motility. Cell 136, 163–174 (2009). Clarifies the molecular mechanism of the Ca2+-dependent regulation of mitochondrial transport.
Cole, D. G. et al. Novel heterotrimeric kinesin-related protein purified from sea urchin eggs. Nature 366, 268–270 (1993).
Kondo, S. et al. KIF3A is a new microtubule-based anterograde motor in the nerve axon. J. Cell Biol. 125, 1095–1107 (1994).
Yamazaki, H., Nakata, T., Okada, Y. & Hirokawa, N. KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport. J. Cell Biol. 130, 1387–1399 (1995).
Wedaman, K. P., Meyer, D. W., Rashid, D. J., Cole, D. G. & Scholey, J. M. Sequence and submolecular localization of the 115-kD accessory subunit of the heterotrimeric kinesin-II (KRP85/95) complex. J. Cell Biol. 132, 371–380 (1996).
Yamazaki, H., Nakata, T., Okada, Y. & Hirokawa, N. Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. Proc. Natl Acad. Sci. USA 93, 8443–8448 (1996).
Hirokawa, N. Stirring up development with the heterotrimeric kinesin KIF3. Traffic 1, 29–34 (2000).
Takeda, S. et al. Kinesin superfamily protein 3 (KIF3) motor transports fodrin-associating vesicles important for neurite building. J. Cell Biol. 148, 1255–1265 (2000).
Taya, S. et al. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3ɛ complex through kinesin-1. J. Neurosci. 27, 15–26 (2007).
Baas, P. W., Deitch, J. S., Black, M. M. & Banker, G. A. Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc. Natl Acad. Sci. USA 85, 8335–8339 (1988).
Nakata, T. & Hirokawa, N. Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head. J. Cell Biol. 162, 1045–1055 (2003). The first description of how the KIF5 motor domain preferentially localizes to the axon. It also shows the importance of microtubule dynamics in this process.
Jacobson, C., Schnapp, B. & Banker, G. A. A change in the selective translocation of the kinesin-1 motor domain marks the initial specification of the axon. Neuron 49, 797–804 (2006).
Witte, H., Neukirchen, D. & Bradke, F. Microtubule stabilization specifies initial neuronal polarization. J. Cell Biol. 180, 619–632 (2008).
Shi, S. H., Cheng, T., Jan, L. Y. & Jan, Y. N. APC and GSK-3β are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity. Curr. Biol. 14, 2025–2032 (2004).
Nishimura, T. et al. Role of the PAR-3–KIF3 complex in the establishment of neuronal polarity. Nature Cell Biol. 6, 328–334 (2004).
Hanada, T., Lin, L., Tibaldi, E. V., Reinherz, E. L. & Chishti, A. H. GAKIN, a novel kinesin-like protein associates with the human homologue of the Drosophila discs large tumor suppressor in T lymphocytes. J. Biol. Chem. 275, 28774–28784 (2000).
Siegrist, S. E. & Doe, C. Q. Microtubule-induced Pins/Gαi cortical polarity in Drosophila neuroblasts. Cell 123, 1323–1335 (2005).
Venkateswarlu, K., Hanada, T. & Chishti, A. H. Centaurin-α1 interacts directly with kinesin motor protein KIF13B. J. Cell Sci. 118, 2471–2484 (2005).
Horiguchi, K., Hanada, T., Fukui, Y. & Chishti, A. H. Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity. J. Cell Biol. 174, 425–436 (2006).
Diefenbach, R. J., Mackay, J. P., Armati, P. J. & Cunningham, A. L. The C-terminal region of the stalk domain of ubiquitous human kinesin heavy chain contains the binding site for kinesin light chain. Biochemistry 37, 16663–16670 (1998).
Skoufias, D. A., Cole, D. G., Wedaman, K. P. & Scholey, J. M. The carboxyl-terminal domain of kinesin heavy chain is important for membrane binding. J. Biol. Chem. 269, 1477–1485 (1994).
Seiler, S. et al. Cargo binding and regulatory sites in the tail of fungal conventional kinesin. Nature Cell Biol. 2, 333–338 (2000).
Bowman, A. B. et al. Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein. Cell 103, 583–594 (2000).
Verhey, K. J. et al. Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol. 152, 959–970 (2001).
Hammond, J. W., Griffin, K., Jih, G. T., Stuckey, J. & Verhey, K. J. Co-operative versus independent transport of different cargoes by Kinesin-1. Traffic 9, 725–741 (2008).
Kelkar, N., Gupta, S., Dickens, M. & Davis, R. J. Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3. Mol. Cell. Biol. 20, 1030–1043 (2000).
Kamal, A., Stokin, G. B., Yang, Z., Xia, C. H. & Goldstein, L. S. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28, 449–459 (2000).
Lazarov, O. et al. Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. J. Neurosci. 25, 2386–2395 (2005).
Inomata, H. et al. A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1. J. Biol. Chem. 278, 22946–22955 (2003).
Terada, S., Kinjo, M. & Hirokawa, N. Oligomeric tubulin in large transporting complex is transported via kinesin in squid giant axons. Cell 103, 141–155 (2000).
Kimura, T., Watanabe, H., Iwamatsu, A. & Kaibuchi, K. Tubulin and CRMP-2 complex is transported via kinesin-1. J. Neurochem. 93, 1371–1382 (2005).
Xia, C. H. et al. Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J. Cell Biol. 161, 55–66 (2003).
Kanai, Y., Dohmae, N. & Hirokawa, N. Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 43, 513–525 (2004). Identifies 42 components of the large RNA-transporting granule that is transported by KIF5 motors.
Dictenberg, J. B., Swanger, S. A., Antar, L. N., Singer, R. H. & Bassell, G. J. A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev. Cell 14, 926–939 (2008).
Setou, M. et al. Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature 417, 83–87 (2002).
Nakagawa, T. et al. Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc. Natl Acad. Sci. USA 94, 9654–9659 (1997).
Setou, M., Nakagawa, T., Seog, D. H. & Hirokawa, N. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288, 1796–1802 (2000). Shows that KIF17 transports NR2B-containing vesicles through the scaffolding protein complex that consists of LIN10, LIN2 and LIN7 in dendrites.
Jo, K., Derin, R., Li, M. & Bredt, D. S. Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J. Neurosci. 19, 4189–4199 (1999).
Kayadjanian, N., Lee, H. S., Pina-Crespo, J. & Heinemann, S. F. Localization of glutamate receptors to distal dendrites depends on subunit composition and the kinesin motor protein KIF17. Mol. Cell. Neurosci. 34, 219–230 (2007).
Chu, P. J., Rivera, J. F. & Arnold, D. B. A role for Kif17 in transport of Kv4. 2. J. Biol. Chem. 281, 365–373 (2006).
Hanlon, D. W., Yang, Z. & Goldstein, L. S. Characterization of KIFC2, a neuronal kinesin superfamily member in mouse. Neuron 18, 439–451 (1997).
Saito, N. et al. KIFC2 is a novel neuron-specific C-terminal type kinesin superfamily motor for dendritic transport of multivesicular body-like organelles. Neuron 18, 425–438 (1997).
Santama, N., Er, C. P., Ong, L. L. & Yu, H. Distribution and functions of kinectin isoforms. J. Cell Sci. 117, 4537–4549 (2004).
Plitz, T. & Pfeffer, K. Intact lysosome transport and phagosome function despite kinectin deficiency. Mol. Cell. Biol. 21, 6044–6055 (2001).
Wozniak, M. J. & Allan, V. J. Cargo selection by specific kinesin light chain 1 isoforms. EMBO J. 25, 5457–5468 (2006).
Stauber, T., Simpson, J. C., Pepperkok, R. & Vernos, I. A role for kinesin-2 in COPI-dependent recycling between the ER and the Golgi complex. Curr. Biol. 16, 2245–2251 (2006).
Echard, A. et al. Interaction of a Golgi-associated kinesin-like protein with Rab6. Science 279, 580–585 (1998).
Harada, A. et al. Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. J. Cell Biol. 141, 51–59 (1998).
Xu, Y. et al. Role of KIFC3 motor protein in Golgi positioning and integration. J. Cell Biol. 158, 293–303 (2002).
Nakagawa, T. et al. A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell 103, 569–581 (2000). Shows that KIF13A transports mannose-6-phosphate receptor from the TGN to the plasma membrane through β1-adaptin.
Lippincott-Schwartz, J., Cole, N. B., Marotta, A., Conrad, P. A. & Bloom, G. S. Kinesin is the motor for microtubule-mediated Golgi-to-ER membrane traffic. J. Cell Biol. 128, 293–306 (1995).
Noda, Y. et al. KIFC3, a microtubule minus end-directed motor for the apical transport of annexin XIIIb-associated triton-insoluble membranes. J. Cell Biol. 155, 77–88 (2001).
Meng, W., Mushika, Y., Ichii, T. & Takeichi, M. Anchorage of microtubule minus ends to adherens junctions regulates epithelial cell–cell contacts. Cell 135, 948–959 (2008). Shows that PLEKHA7 and nezha anchor microtubule minus ends to apical zonula adherens in epithelial cells and recruit KIFC3 to stabilize apical zonula adherens.
Jaulin, F., Xue, X., Rodriguez-Boulan, E. & Kreitzer, G. Polarization-dependent selective transport to the apical membrane by KIF5B in MDCK cells. Dev. Cell 13, 511–522 (2007).
Nakata, T. & Hirokawa, N. Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport. J. Cell Biol. 131, 1039–1053 (1995).
Gross, S. P., Welte, M. A., Block, S. M. & Wieschaus, E. F. Coordination of opposite-polarity microtubule motors. J. Cell Biol. 156, 715–724 (2002).
Jordens, I., Marsman, M., Kuijl, C. & Neefjes, J. Rab proteins, connecting transport and vesicle fusion. Traffic 6, 1070–1077 (2005).
Bananis, E., Murray, J. W., Stockert, R. J., Satir, P. & Wolkoff, A. W. Microtubule and motor-dependent endocytic vesicle sorting in vitro. J. Cell Biol. 151, 179–186 (2000).
Imamura, T. et al. Insulin-induced GLUT4 translocation involves protein kinase C-λ-mediated functional coupling between Rab4 and the motor protein kinesin. Mol. Cell. Biol. 23, 4892–4900 (2003).
Bananis, E. et al. Microtubule-dependent movement of late endocytic vesicles in vitro: requirements for dynein and kinesin. Mol. Biol. Cell 15, 3688–3697 (2004).
Brown, C. L. et al. Kinesin-2 is a motor for late endosomes and lysosomes. Traffic 6, 1114–1124 (2005).
Schonteich, E. et al. The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling. J. Cell Sci. 121, 3824–3833 (2008).
Hoepfner, S. et al. Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 121, 437–450 (2005). Shows that KIF16B binds to PtdIns(3,4,5)P 3 -containing endosomes and fixes EGFs and EGF receptors beneath the plasma membrane through its plus end-directed motility.
Kozminski, K. G., Johnson, K. A., Forscher, P. & Rosenbaum, J. L. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc. Natl Acad. Sci. USA 90, 5519–5523 (1993).
Cole, D. G. et al. 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 (1998).
Ou, G., Blacque, O. E., Snow, J. J., Leroux, M. R. & Scholey, J. M. Functional coordination of intraflagellar transport motors. Nature 436, 583–587 (2005). Reveals that kinesin 2 and OSM3 work partially synergistically for the transport of particle complexes to the tips of flagella.
Jenkins, P. M. et al. Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17. Curr. Biol. 16, 1211–1216 (2006).
Dietrich, K. A. et al. The kinesin-1 motor protein is regulated by a direct interaction of its head and tail. Proc. Natl Acad. Sci. USA 105, 8938–8943 (2008).
Wong, Y. L., Dietrich, K. A., Naber, N., Cooke, R. & Rice, S. E. The kinesin-1 tail conformationally restricts the nucleotide pocket. Biophys. J. 96, 2799–2807 (2009).
Hammond, J. W. et al. Mammalian kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition. PLoS Biol. 7, e72 (2009).
Sato-Yoshitake, R., Yorifuji, H., Inagaki, M. & Hirokawa, N. The phosphorylation of kinesin regulates its binding to synaptic vesicles. J. Biol. Chem. 267, 23930–23936 (1992).
Hollenbeck, P. J. Phosphorylation of neuronal kinesin heavy and light chains in vivo. J. Neurochem. 60, 2265–2275 (1993).
Morfini, G., Szebenyi, G., Elluru, R., Ratner, N. & Brady, S. T. Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J. 21, 281–293 (2002).
Guillaud, L., Wong, R. & Hirokawa, N. Disruption of KIF17–Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin-cargo release. Nature Cell Biol. 10, 19–29 (2008). Shows that CaMKII-dependent phosphorylation of the cargo-binding domain of KIF17 causes unloading of NR2B-carrying vesicles.
Morfini, G. et al. JNK mediates pathogenic effects of polyglutamine-expanded androgen receptor on fast axonal transport. Nature Neurosci. 9, 907–916 (2006).
Stagi, M., Gorlovoy, P., Larionov, S., Takahashi, K. & Neumann, H. Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway. FASEB J. 20, 2573–2575 (2006).
Horiuchi, D. et al. Control of a kinesin–cargo linkage mechanism by JNK pathway kinases. Curr. Biol. 17, 1313–1317 (2007).
Gindhart, J. G. et al. The kinesin-associated protein UNC-76 is required for axonal transport in the Drosophila nervous system. Mol. Biol. Cell 14, 3356–3365 (2003).
Ogura, K. et al. Caenorhabditis elegans unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase. Genes Dev. 8, 2389–2400 (1994).
Midorikawa, R., Takei, Y. & Hirokawa, N. KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity. Cell 125, 371–383 (2006). Functional analysis of Kif4 - knockout neurons reveals a role for KIF4 in activity-dependent neuronal survival.
Zerial, M. & McBride, H. Rab proteins as membrane organizers. Nature Rev. Mol. Cell Biol. 2, 107–117 (2001).
Goud, B., Zahraoui, A., Tavitian, A. & Saraste, J. Small GTP-binding protein associated with Golgi cisternae. Nature 345, 553–556 (1990).
Hill, E., Clarke, M. & Barr, F. A. The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis. EMBO J. 19, 5711–5719 (2000).
Fontijn, R. D. et al. The human kinesin-like protein RB6K is under tight cell cycle control and is essential for cytokinesis. Mol. Cell. Biol. 21, 2944–2955 (2001).
Chavrier, P., Parton, R. G., Hauri, H. P., Simons, K. & Zerial, M. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 62, 317–329 (1990).
Nielsen, E., Severin, F., Backer, J. M., Hyman, A. A. & Zerial, M. Rab5 regulates motility of early endosomes on microtubules. Nature Cell Biol. 1, 376–382 (1999).
Niwa, S., Tanaka, Y. & Hirokawa, N. KIF1Bβ- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through DENN/MADD. Nature Cell Biol. 10, 1269–1279 (2008). The binding of GTP-bound RAB3 to KIF1Bβ and KIF1A through DENN/MADD was shown to be required for the transport of RAB3-carrying vesicles.
Klopfenstein, D. R., Tomishige, M., Stuurman, N. & Vale, R. D. Role of phosphatidylinositol(4,5) bisphosphate organization in membrane transport by the Unc104 kinesin motor. Cell 109, 347–358 (2002).
Klopfenstein, D. R. & Vale, R. D. The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans. Mol. Biol. Cell 15, 3729–3739 (2004).
De Robertis, E. D. & Bennett, H. S. Some features of the submicroscopic morphology of synapses in frog and earthworm. J. Biophys. Biochem. Cytol. 1, 47–58 (1955).
Rintoul, G. L., Filiano, A. J., Brocard, J. B., Kress, G. J. & Reynolds, I. J. Glutamate decreases mitochondrial size and movement in primary forebrain neurons. J. Neurosci. 23, 7881–7888 (2003).
Yi, M., Weaver, D. & Hajnoczky, G. Control of mitochondrial motility and distribution by the calcium signal: a homeostatic circuit. J. Cell Biol. 167, 661–672 (2004).
Hollenbeck, P. J. & Saxton, W. M. The axonal transport of mitochondria. J. Cell Sci. 118, 5411–5419 (2005).
Chang, D. T., Honick, A. S. & Reynolds, I. J. Mitochondrial trafficking to synapses in cultured primary cortical neurons. J. Neurosci. 26, 7035–7045 (2006).
Stowers, R. S., Megeath, L. J., Górska-Andrzejak, J., Meinertzhagen, I. A. & Schwarz, T. L. Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36, 1063–1077 (2002).
Guo, X. et al. The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 47, 379–393 (2005).
Macaskill, A. F. et al. Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Neuron 61, 541–555 (2009).
Nonaka, S. et al. Randomization of left–right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829–837 (1998). The first paper to propose the nodal-flow hypothesis of left–right determination in the Kif3b - knockout mouse.
Yonekawa, Y. et al. Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice. J. Cell Biol. 141, 431–441 (1998).
Takeda, S. et al. Left–right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A−/− mice analysis. J. Cell Biol. 145, 825–836 (1999).
Marszalek, J. R., Ruiz-Lozano, P., Roberts, E., Chien, K. R. & Goldstein, L. S. Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc. Natl Acad. Sci. USA 96, 5043–5048 (1999).
Marszalek, J. R. et al. Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell 102, 175–187 (2000).
Wong, R. W., Setou, M., Teng, J., Takei, Y. & Hirokawa, N. Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice. Proc. Natl Acad. Sci. USA 99, 14500–14505 (2002). The Kif17 -transgenic mouse revealed the in vivo role of KIF17 in the enhancement of learning and memory.
Homma, N. et al. Kinesin superfamily protein 2A (KIF2A) functions in suppression of collateral branch extension. Cell 114, 229–239 (2003).
Lin, F. et al. Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc. Natl Acad. Sci. USA 100, 5286–5291 (2003).
Teng, J. et al. The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium. Nature Cell Biol. 7, 474–482 (2005). Analysis of Kap3 conditional knockout mice suggests a signal transduction cascade is modulated by the KIF-mediated transport of signalling molecules, and that KIF3 suppresses tumorigenesis.
Kolpakova-Hart, E., Jinnin, M., Hou, B., Fukai, N. & Olsen, B. R. Kinesin-2 controls development and patterning of the vertebrate skeleton by Hedgehog- and Gli3-dependent mechanisms. Dev. Biol. 309, 273–284 (2007).
Koyama, E. et al. Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis. Development 134, 2159–2169 (2007).
Haycraft, C. J. et al. Intraflagellar transport is essential for endochondral bone formation. Development 134, 307–316 (2007).
Davenport, J. R. et al. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr. Biol. 17, 1586–1594 (2007).
Okada, Y. et al. Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol. Cell 4, 459–468 (1999).
Tanaka, Y., Okada, Y. & Hirokawa, N. FGF-induced vesicular release of sonic hedgehog and retinoic acid in leftward nodal flow is critical for left–right determination. Nature 435, 172–177 (2005).
Okada, Y., Takeda, S., Tanaka, Y., Belmonte, J. C. & Hirokawa, N. Mechanism of nodal flow: a conserved symmetry breaking event in left–right axis determination. Cell 121, 633–644 (2005).
Hirokawa, N., Tanaka, Y., Okada, Y. & Takeda, S. Nodal flow and the generation of left-right asymmetry. Cell 125, 33–45 (2006).
Huangfu, D. et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83–87 (2003).
Chevalier-Larsen, E. & Holzbaur, E. L. Axonal transport and neurodegenerative disease. Biochim. Biophys. Acta 1762, 1094–1108 (2006).
Reid, E. et al. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am. J. Hum. Genet. 71, 1189–1194 (2002).
Marszalek, J. R., Weiner, J. A., Farlow, S. J., Chun, J. & Goldstein, L. S. Novel dendritic kinesin sorting identified by different process targeting of two related kinesins: KIF21A and KIF21B. J. Cell Biol. 145, 469–479 (1999).
Yamada, K. et al. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nature Genet. 35, 318–321 (2003).
Shen, X. et al. Interaction of brefeldin A-inhibited guanine nucleotide-exchange protein (BIG) 1 and kinesin motor protein KIF21A. Proc. Natl Acad. Sci. USA 105, 18788–18793 (2008).
Sekine, Y. et al. A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally. J. Cell Biol. 127, 187–201 (1994).
Peretti, D., Peris, L., Rosso, S., Quiroga, S. & Cáceres, A. Evidence for the involvement of KIF4 in the anterograde transport of L1-containing vesicles. J. Cell Biol. 149, 141–152 (2000).
Puthanveettil, S. V. et al. A new component in synaptic plasticity: upregulation of kinesin in the neurons of the gill-withdrawal reflex. Cell 135, 960–973 (2008). Analyses the role of KIF5 in the A. mollusca gill withdrawal reflex.
Lawrence, C. J., Malmberg, R. L., Muszynski, M. G. & Dawe, R. K. Maximum likelihood methods reveal conservation of function among closely related kinesin families. J. Mol. Evol. 54, 42–53 (2002).
Miki, H., Setou, M., Hirokawa, N., Group, R. G. & Members, G. Kinesin superfamily proteins (KIFs) in the mouse transcriptome. Genome Res. 13, 1455–1465 (2003).
Miki, H., Okada, Y. & Hirokawa, N. Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol. 15, 467–476 (2005).
Hirokawa, N., Okada, Y. & Tanaka, Y. Fluid dynamic mechanism responsible for breaking the left–right symmetry of the human body: the nodal flow. Ann. Rev. Fluid Mech. 41, 53–72 (2009).
The authors thank H. Fukuda, H. Sato and all other members of the Hirokawa laboratory for their technical assistance, support and discussion. This work was supported by a Grant-in-Aid for Specially Promoted Research to N. H. and a global COE programme to the University of Tokyo from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
- WD40 repeat
A protein motif that is composed of a 40 amino acid repeat that forms a blade of the characteristic β-propeller structure. Proteins that contain WD40 repeats participate in G protein-mediated signal transduction, transcriptional regulation, RNA processing and regulation of vesicle formation and trafficking.
A glycoprotein of 38 kDa that is localized to synaptic vesicle membranes.
One of a group of Ca2+-binding proteins that are involved in the secretion of granules and vesicles, especially in the nervous system.
Occurs when a diploid organism has only a single functional copy of a gene that does not produce enough of a gene product to bring about a wild-type condition. This leads to an abnormal or diseased state.
An integral synaptic vesicle protein of 18 kDa that is involved in the formation of the SNARE complex in exocytosis. Synaptobrevin is a major target of cleavage by tetanus toxin.
- Armadillo repeat
A protein–protein interaction consensus stretch of 40 amino acids.
- Tetratricopeptide motif
A loosely conserved domain of 30–40 amino acids that is involved in protein–protein interactions.
- Voltage-gated potassium channel
A class of transmembrane channel that senses the electrical potential across the plasma membrane to open and admit K+ flow through the membrane.
- Apical transport
A mode of organelle transport in polarized cells towards the apical surface of the cell.
- Zonula adherens
A cell–cell adherens junction that forms a circumferential belt around the apical pole of epithelial cells.
An organelle that contains melanin, a common light-absorbing pigment.
An intracellular lipid bilayer membrane that surrounds small spaces, for example to form vesicles and membrane organelles. Endomembranes fuse with and are removed from the plasma membrane by exocytosis and endocytosis, respectively.
- PX domain
(Phox homology domain). A lipid and protein interaction domain that consists of 100–130 amino acids and is defined by sequences that are found in two components of the phagocyte NADPH oxidase (phox) complex.
- Pleckstrin homology (PH) domain
A sequence of 100 amino acids that is present in many signalling molecules and binds to lipid products of phosphoinositide kinases.
- EF hand
A protein motif that might bind to Ca2+.
- Planar cell polarity
A one-dimensional polarity on a cell sheet that is essential for many aspects of the development of tissues.
- Hereditary spastic paraplegia
A human progressive neuronal disease of hereditary origin that is characterized by increasing weakness and stiffness of the legs.
- Laminary defect
A developmental defect of the brain that disorganizes the laminary structure of the cortex.
- Long-term facilitation
A mode of synaptic plasticity in which stimulation results in a persistent increase in synaptic transmission.
About this article
Cite this article
Hirokawa, N., Noda, Y., Tanaka, Y. et al. Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10, 682–696 (2009). https://doi.org/10.1038/nrm2774
This article is cited by
ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle
Journal of Experimental & Clinical Cancer Research (2023)
Journal of Human Genetics (2023)
Cellular and Molecular Life Sciences (2023)
Human Genetics (2023)
Journal of Biological Physics (2023)