Biochemistry (Moscow)

, Volume 82, Issue 7, pp 803–815 | Cite as

Intracellular cargo transport by kinesin-3 motors

  • N. Siddiqui
  • A. StraubeEmail author
Open Access


Intracellular transport along microtubules enables cellular cargoes to efficiently reach the extremities of large, eukaryotic cells. While it would take more than 200 years for a small vesicle to diffuse from the cell body to the growing tip of a one-meter long axon, transport by a kinesin allows delivery in one week. It is clear from this example that the evolution of intracellular transport was tightly linked to the development of complex and macroscopic life forms. The human genome encodes 45 kinesins, 8 of those belonging to the family of kinesin-3 organelle transporters that are known to transport a variety of cargoes towards the plus end of microtubules. However, their mode of action, their tertiary structure, and regulation are controversial. In this review, we summarize the latest developments in our understanding of these fascinating molecular motors.


molecular motors microtubule-based transport kinesin autoinhibition intracellular transport Unc104/KIF1 cargo trafficking 


  1. 1.
    Cross, R. A. (2016) Review: Mechanochemistry of the kinesin-1 ATPase, Biopolymers, 105, 476–482.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Lawrence, C. J., Dawe, R. K., Christie, K. R., Cleveland, D. W., Dawson, S. C., Endow, S. A., Goldstein, L. S., Goodson, H. V., Hirokawa, N., Howard, J., Malmberg, R. L., Mcintosh, J. R., Miki, H., Mitchison, T. J., Okada, Y., Reddy, A. S., Saxton, W. M., Schliwa, M., Scholey, J. M., Vale, R. D., Walczak, C. E., and Wordeman, L. (2004) A standardized kinesin nomenclature, J. Cell Biol., 167, 19–22.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Wickstead, B., Gull, K., and Richards, T. A. (2010) Patterns of kinesin evolution reveal a complex ancestral eukaryote with a multifunctional cytoskeleton, BMC Evol. Biol., 10,110.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Hall, D. H., and Hedgecock, E. M. (1991) Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans, Cell, 65, 837–847.PubMedCrossRefGoogle Scholar
  5. 5.
    Otsuka, A. J., Jeyaprakash, A., Garcia-Anoveros, J., Tang, L. Z., Fisk, G., Hartshorne, T., Franco, R., and Born, T. (1991) The C. elegans unc-104 gene encodes a putative kinesin heavy chain-like protein, Neuron, 6, 113–122.PubMedCrossRefGoogle Scholar
  6. 6.
    Pollock, N., De Hostos, E. L., Turck, C. W., and Vale, R. D. (1999) Reconstitution of membrane transport powered by a novel dimeric kinesin motor of the Unc104/KIF1A family purified from Dictyostelium, J. Cell Biol., 147, 493–506.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Wedlich-Soldner, R. (2002) A balance of KIF1A-like kinesin and dynein organizes early endosomes in the fungus Ustilago maydis, EMBO J., 21, 2946–2957.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Seidel, C., Moreno-Velasquez, S. D., Riquelme, M., and Fischer, R. (2013) Neurospora crassa NKIN2, a kinesin-3 motor, transports early endosomes and is required for polarized growth, Eukaryot. Cell, 12, 1020–1032.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Zekert, N., and Fischer, R. (2009) The Aspergillus nidulans kinesin-3 UncA motor moves vesicles along a subpopulation of microtubules, Mol. Biol. Cell, 20, 673–684.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Kratchmarov, R., Kramer, T., Greco, T. M., Taylor, M. P., Ch’ng, T. H., Cristea, I. M., and Enquist, L. W. (2013) Glycoproteins gE and gI are required for efficient KIF1A-dependent anterograde axonal transport of alphaher-pesvirus particles in neurons, J. Virol., 87, 9431–9440.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Lo, K. Y., Kuzmin, A., Unger, S. M., Petersen, J. D., and Silverman, M. A. (2011) KIF1A is the primary anterograde motor protein required for the axonal transport of dense-core vesicles in cultured hippocampal neurons, Neurosci. Lett., 491, 168–173.PubMedCrossRefGoogle Scholar
  12. 12.
    Nangaku, M., Sato-Yoshitake, R., Okada, Y., Noda, Y., Takemura, R., Yamazaki, H., and Hirokawa, N. (1994) KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria, Cell, 79, 1209–1220.PubMedCrossRefGoogle Scholar
  13. 13.
    Niwa, S., Tanaka, Y., and Hirokawa, N. (2008) KIF1Bbeta-and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through DENN/MADD, Nat. Cell Biol., 10, 1269–1279.PubMedCrossRefGoogle Scholar
  14. 14.
    Okada, Y., Yamazaki, H., Sekine-Aizawa, Y., and Hirokawa, N. (1995) The neuron-specific kinesin super-family protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors, Cell, 81, 769–780.PubMedCrossRefGoogle Scholar
  15. 15.
    Theisen, U., Straube, E., and Straube, A. (2012) Directional persistence of migrating cells requires Kif1C-mediated stabilization of trailing adhesions, Dev. Cell, 23, 1153–1166.PubMedCrossRefGoogle Scholar
  16. 16.
    Wagner, O. I., Esposito, A., Kohler, B., Chen, C. W., Shen, C. P., Wu, G. H., Butkevich, E., Mandalapu, S., Wenzel, D., Wouters, F. S., and Klopfenstein, D. R. (2009) Synaptic scaffolding protein SYD-2 clusters and activates kinesin-3 UNC-104 in C. elegans, Proc. Natl. Acad. Sci. USA, 106, 19605–19610.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Wozniak, M. J., Melzer, M., Dorner, C., Haring, H. U., and Lammers, R. (2005) The novel protein KBP regulates mitochondria localization by interaction with a kinesin-like protein, BMC Cell Biol., 6,35.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Miki, H., Okada, Y., and Hirokawa, N. (2005) Analysis of the kinesin superfamily: insights into structure and function, Trends Cell Biol., 15, 467–476.PubMedCrossRefGoogle Scholar
  19. 19.
    Fuchs, F. (2004) Role of Unc104/KIF1-related motor proteins in mitochondrial transport in neurospora crassa, Mol. Biol. Cell, 16, 153–161.PubMedCrossRefGoogle Scholar
  20. 20.
    Dor, T., Cinnamon, Y., Raymond, L., Shaag, A., Bouslam, N., Bouhouche, A., Gaussen, M., Meyer, V., Durr, A., Brice, A., Benomar, A., Stevanin, G., Schuelke, M., and Edvardson, S. (2014) KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction, J. Med. Genet., 51, 137–142.PubMedCrossRefGoogle Scholar
  21. 21.
    Yonekawa, Y., Harada, A., Okada, Y., Funakoshi, T., Kanai, Y., Takei, Y., Terada, S., Noda, T., and Hirokawa, N. (1998) Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice, J. Cell Biol., 141, 431–441.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Caballero Oteyza, A., Battaloglu, E., Ocek, L., Lindig, T., Reichbauer, J., Rebelo, A. P., Gonzalez, M. A., Zorlu, Y., Ozes, B., Timmann, D., Bender, B., Woehlke, G., Zuchner, S., Schols, L., and Schule, R. (2014) Motor protein mutations cause a new form of hereditary spastic paraplegia, Neurology, 82, 2007–2016.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Aulchenko, Y. S., Hoppenbrouwers, I. A., Ramagopalan, S. V., Broer, L., Jafari, N., Hillert, J., Link, J., Lundstrom, W., Greiner, E., Dessa Sadovnick, A., Goossens, D., Van Broeckhoven, C., Del-Favero, J., Ebers, G. C., Oostra, B. A., Van Duijn, C. M., and Hintzen, R. Q. (2008) Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis, Nat. Genet., 40, 1402–1403.PubMedCrossRefGoogle Scholar
  24. 24.
    Kern, J. V., Zhang, Y. V., Kramer, S., Brenman, J. E., and Rasse, T. M. (2013) The kinesin-3, Unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila, Genetics, 195, 59–72.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Lenz, J. H., Schuchardt, I., Straube, A., and Steinberg, G. (2006) A dynein loading zone for retrograde endosome motility at microtubule plus-ends, EMBO J., 25, 2275–2286.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Torres, J. Z., Summers, M. K., Peterson, D., Brauer, M. J., Lee, J., Senese, S., Gholkar, A. A., Lo, Y. C., Lei, X., Jung, K., Anderson, D. C., Davis, D. P., Belmont, L., and Jackson, P. K. (2011) The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly, Cell, 147, 1309–1323.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Sagona, A. P., Nezis, I. P., Pedersen, N. M., Liestol, K., Poulton, J., Rusten, T. E., Skotheim, R. I., Raiborg, C., and Stenmark, H. (2010) PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody, Nat. Cell Biol., 12, 362–371.PubMedCrossRefGoogle Scholar
  28. 28.
    Drerup, C. M., Lusk, S., and Nechiporuk, A. (2016) Kif1B interacts with KBP to promote axon elongation by localizing a microtubule regulator to growth cones, J. Neurosci., 36, 7014–7026.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Fehling, S. K., Noda, T., Maisner, A., Lamp, B., Conzelmann, K. K., Kawaoka, Y., Klenk, H. D., Garten, W., and Strecker, T. (2013) The microtubule motor protein KIF13A is involved in intracellular trafficking of the Lassa virus matrix protein Z, Cell. Microbiol., 15, 315–334.PubMedCrossRefGoogle Scholar
  30. 30.
    Horiguchi, K., Hanada, T., Fukui, Y., and Chishti, A. H. (2006) Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity, J. Cell Biol., 174, 425–436.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Ueno, H., Huang, X., Tanaka, Y., and Hirokawa, N. (2011) KIF16B/Rab14 molecular motor complex is critical for early embryonic development by transporting FGF receptor, Dev. Cell, 20, 60–71.PubMedCrossRefGoogle Scholar
  32. 32.
    Tanaka, Y., Niwa, S., Dong, M., Farkhondeh, A., Wang, L., Zhou, R., and Hirokawa, N. (2016) The molecular motor KIF1A transports the TrkA neurotrophin receptor and is essential for sensory neuron survival and function, Neuron, 90, 1215–1229.PubMedCrossRefGoogle Scholar
  33. 33.
    Hung, C. O., and Coleman, M. P. (2016) KIF1A mediates axonal transport of BACE1 and identification of independently moving cargoes in living SCG neurons, Traffic, 17, 1155–1167.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Shin, H., Wyszynski, M., Huh, K. H., Valtschanoff, J. G., Lee, J. R., Ko, J., Streuli, M., Weinberg, R. J., Sheng, M., and Kim, E. (2003) Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha, J. Biol. Chem., 278, 11393–11401.PubMedCrossRefGoogle Scholar
  35. 35.
    Matsushita, M., Tanaka, S., Nakamura, N., Inoue, H., and Kanazawa, H. (2004) A novel kinesin-like protein, KIF1Bbeta3 is involved in the movement of lysosomes to the cell periphery in non-neuronal cells, Traffic, 5, 140–151.PubMedCrossRefGoogle Scholar
  36. 36.
    Zhou, R., Niwa, S., Guillaud, L., Tong, Y., and Hirokawa, N. (2013) A molecular motor, KIF13A, controls anxiety by transporting the serotonin type 1A receptor, Cell Rep., 3, 509–519.PubMedCrossRefGoogle Scholar
  37. 37.
    Nakagawa, T., Setou, M., Seog, D., Ogasawara, K., Dohmae, N., Takio, K., and Hirokawa, N. (2000) A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex, Cell, 103, 569–581.PubMedCrossRefGoogle Scholar
  38. 38.
    Yamada, K. H., Hanada, T., and Chishti, A. H. (2007) The effector domain of human Dlg tumor suppressor acts as a switch that relieves autoinhibition of kinesin-3 motor GAKIN/KIF13B, Biochemistry, 46, 10039–10045.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Yamada, K. H., Nakajima, Y., Geyer, M., Wary, K. K., Ushio-Fukai, M., Komarova, Y., and Malik, A. B. (2014) KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2, J. Cell Sci., 127, 4518–4530.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Xing, B. M., Yang, Y. R., Du, J. X., Chen, H. J., Qi, C., Huang, Z. H., Zhang, Y., and Wang, Y. (2012) Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B, J. Neurosci., 32, 14709–14721.PubMedCrossRefGoogle Scholar
  41. 41.
    Bielska, E., Schuster, M., Roger, Y., Berepiki, A., Soanes, D. M., Talbot, N. J., and Steinberg, G. (2014) Hook is an adapter that coordinates kinesin-3 and dynein cargo attachment on early endosomes, J. Cell Biol., 204, 989–1007.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Tanaka, K., Sugiura, Y., Ichishita, R., Mihara, K., and Oka, T. (2011) KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells, J. Cell Sci., 124, 2457–2465.PubMedCrossRefGoogle Scholar
  43. 43.
    Peden, E. M., and Barr, M. M. (2005) The KLP-6 kinesin is required for male mating behaviors and polycystin localization in Caenorhabditis elegans, Curr. Biol., 15, 394–404.PubMedCrossRefGoogle Scholar
  44. 44.
    Monteiro, M. I., Ahlawat, S., Kowalski, J. R., Malkin, E., Koushika, S. P., and Juo, P. (2012) The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans, Mol. Biol. Cell, 23, 3647–3662.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Westerholm-Parvinen, A., Vernos, I., and Serrano, L. (2000) Kinesin subfamily UNC104 contains a FHA domain: boundaries and physicochemical characterization, FEBS Lett., 486, 285–290.PubMedCrossRefGoogle Scholar
  46. 46.
    Endow, S. A. (1999) Determinants of molecular motor directionality, Nat. Cell Biol., 1, E163–167.CrossRefGoogle Scholar
  47. 47.
    Vale, R. D., Case, R., Sablin, E., Hart, C., and Fletterick, R. (2000) Searching for kinesin’s mechanical amplifier, Philos. Trans. R Soc. Lond. B Biol. Sci., 355, 449–457.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Okada, Y., and Hirokawa, N. (1999) A processive single-headed motor: kinesin superfamily protein KIF1A, Science, 283, 1152–1157.PubMedCrossRefGoogle Scholar
  49. 49.
    Okada, Y., and Hirokawa, N. (2000) Mechanism of the single-headed processivity: diffusional anchoring between the K-loop of kinesin and the C terminus of tubulin, Proc. Natl. Acad. Sci. USA, 97, 640–645.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Soppina, V., and Verhey, K. J. (2014) The family-specific K-loop influences the microtubule on-rate but not the superpro-cessivity of kinesin-3 motors, Mol. Biol. Cell, 25, 2161–2170.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rogers, K. R., Weiss, S., Crevel, I., Brophy, P. J., Geeves, M., and Cross, R. (2001) KIF1D is a fast non-processive kinesin that demonstrates novel K-loop-dependent mechanochemistry, EMBO J., 20, 5101–5113.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Matsushita, M., Yamamoto, R., Mitsui, K., and Kanazawa, H. (2009) Altered motor activity of alternative splice variants of the mammalian kinesin-3 protein KIF1B, Traffic, 10, 1647–1654.PubMedCrossRefGoogle Scholar
  53. 53.
    Scarabelli, G., Soppina, V., Yao, X. Q., Atherton, J., Moores, C. A., Verhey, K. J., and Grant, B. J. (2015) Mapping the processivity determinants of the kinesin-3 motor domain, Biophys. J., 109, 1537–1540.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Atherton, J., Farabella, I., Yu, I. M., Rosenfeld, S. S., Houdusse, A., Topf, M., and Moores, C. A. (2014) Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins, Elife, 3, e03680.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Peckham, M. (2011) Coiled coils and SAH domains in cytoskeletal molecular motors, Biochem. Soc. Trans., 39, 1142–1148.PubMedCrossRefGoogle Scholar
  56. 56.
    Dorner, C., Ullrich, A., Haring, H. U., and Lammers, R. (1999) The kinesin-like motor protein KIF1C occurs in intact cells as a dimer and associates with proteins of the 14-3-3 family, J. Biol. Chem., 274, 33654–33660.PubMedCrossRefGoogle Scholar
  57. 57.
    Hammond, J. W., Cai, D., Blasius, T. L., Li, Z., Jiang, Y., Jih, G. T., Meyhofer, E., and Verhey, K. J. (2009) Mammalian kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition, PLoS Biol., 7, e72.PubMedCrossRefGoogle Scholar
  58. 58.
    Soppina, V., Norris, S. R., Dizaji, A. S., Kortus, M., Veatch, S., Peckham, M., and Verhey, K. J. (2014) Dimerization of mammalian kinesin-3 motors results in superprocessive motion, Proc. Natl. Acad. Sci. USA, 111, 5562–5567.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Li, J., Lee, G. I., Van Doren, S. R., and Walker, J. C. (2000) The FHA domain mediates phosphoprotein interactions, J. Cell Sci., 113 (Pt. 23), 4143–4149.PubMedGoogle Scholar
  60. 60.
    Hammet, A., Pike, B. L., Mcnees, C. J., Conlan, L. A., Tenis, N., and Heierhorst, J. (2003) FHA domains as phospho-threonine binding modules in cell signaling, IUBMB Life, 55, 23–27.PubMedCrossRefGoogle Scholar
  61. 61.
    Durocher, D., and Jackson, S. P. (2002) The FHA domain, FEBS Lett., 513, 58–66.PubMedCrossRefGoogle Scholar
  62. 62.
    Watters, J. W., Dewar, K., Lehoczky, J., Boyartchuk, V., and Dietrich, W. F. (2001) Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor, Curr. Biol., 11, 1503–1511.PubMedCrossRefGoogle Scholar
  63. 63.
    Xue, X., Jaulin, F., Espenel, C., and Kreitzer, G. (2010) PH-domain-dependent selective transport of p75 by kinesin-3 family motors in non-polarized MDCK cells, J. Cell Sci., 123, 1732–1741.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Klopfenstein, D. R., Tomishige, M., Stuurman, N., and Vale, R. D. (2002) Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor, Cell, 109, 347–358.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Blatner, N. R., Wilson, M. I., Lei, C., Hong, W., Murray, D., Williams, R. L., and Cho, W. (2007) The structural basis of novel endosome anchoring activity of KIF16B kinesin, EMBO J., 26, 3709–3719.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Hoepfner, S., Severin, F., Cabezas, A., Habermann, B., Runge, A., Gillooly, D., Stenmark, H., and Zerial, M. (2005) Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B, Cell, 121, 437–450.PubMedCrossRefGoogle Scholar
  67. 67.
    Steinmetz, M. O., and Akhmanova, A. (2008) Capturing protein tails by CAP-Gly domains, Trends Biochem. Sci., 33, 535–545.PubMedCrossRefGoogle Scholar
  68. 68.
    Williamson, M. P. (1994) The structure and function of proline-rich regions in proteins, Biochem. J., 297 (Pt. 2), 249–260.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Schlager, M. A., Kapitein, L. C., Grigoriev, I., Burzynski, G. M., Wulf, P. S., Keijzer, N., De Graaff, E., Fukuda, M., Shepherd, I. T., Akhmanova, A., and Hoogenraad, C. C. (2010) Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis, EMBO J., 29, 1637–1651.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Lee, P. L., Ohlson, M. B., and Pfeffer, S. R. (2015) Rab6 regulation of the kinesin family KIF1C motor domain contributes to Golgi tethering, Elife,4.Google Scholar
  71. 71.
    Okada, Y., Higuchi, H., and Hirokawa, N. (2003) Processivity of the single-headed kinesin KIF1A through biased binding to tubulin, Nature, 424, 574–577.PubMedCrossRefGoogle Scholar
  72. 72.
    Oriola, D., and Casademunt, J. (2013) Cooperative force generation of KIF1A Brownian motors, Phys. Rev. Lett., 111, 048103.PubMedCrossRefGoogle Scholar
  73. 73.
    Al-Bassam, J., Cui, Y., Klopfenstein, D., Carragher, B. O., Vale, R. D., and Milligan, R. A. (2003) Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer motor transition, J. Cell Biol., 163, 743–753.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Rashid, D. J., Bononi, J., Tripet, B. P., Hodges, R. S., and Pierce, D. W. (2005) Monomeric and dimeric states exhibited by the kinesin-related motor protein KIF1A, J. Pept. Res., 65, 538–549.PubMedCrossRefGoogle Scholar
  75. 75.
    Tomishige, M., Klopfenstein, D. R., and Vale, R. D. (2002) Conversion of Unc104/KIF1A kinesin into a processive motor after dimerization, Science, 297, 2263–2267.PubMedCrossRefGoogle Scholar
  76. 76.
    Hirokawa, N., Pfister, K. K., Yorifuji, H., Wagner, M. C., Brady, S. T., and Bloom, G. S. (1989) Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration, Cell, 56, 867–878.PubMedCrossRefGoogle Scholar
  77. 77.
    Hackney, D. D., Levitt, J. D., and Suhan, J. (1992) Kinesin undergoes a 9 S to 6 S conformational transition, J. Biol. Chem., 267, 8696–8701.PubMedGoogle Scholar
  78. 78.
    Friedman, D. S., and Vale, R. D. (1999) Single-molecule analysis of kinesin motility reveals regulation by the cargo-binding tail domain, Nat. Cell Biol., 1, 293–297.PubMedCrossRefGoogle Scholar
  79. 79.
    Stock, M. F., Guerrero, J., Cobb, B., Eggers, C. T., Huang, T. G., Li, X., and Hackney, D. D. (1999) Formation of the compact confomer of kinesin requires a COOH-terminal heavy chain domain and inhibits microtubule-stimulated ATPase activity, J. Biol. Chem., 274, 14617–14623.PubMedCrossRefGoogle Scholar
  80. 80.
    Coy, D. L., Hancock, W. O., Wagenbach, M., and Howard, J. (1999) Kinesin’s tail domain is an inhibitory regulator of the motor domain, Nat. Cell Biol., 1, 288–292.PubMedCrossRefGoogle Scholar
  81. 81.
    Hirokawa, N., and Noda, Y. (2008) Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics, Physiol. Rev., 88, 1089–1118.PubMedCrossRefGoogle Scholar
  82. 82.
    Huo, L., Yue, Y., Ren, J., Yu, J., Liu, J., Yu, Y., Ye, F., Xu, T., Zhang, M., and Feng, W. (2012) The CC1-FHA tandem as a central hub for controlling the dimerization and activation of kinesin-3 KIF1A, Structure, 20, 1550–1561.PubMedCrossRefGoogle Scholar
  83. 83.
    Yue, Y., Sheng, Y., Zhang, H. N., Yu, Y., Huo, L., Feng, W., and Xu, T. (2013) The CC1-FHA dimer is essential for KIF1A-mediated axonal transport of synaptic vesicles in C. elegans, Biochem. Biophys. Res. Commun., 435, 441–446.PubMedCrossRefGoogle Scholar
  84. 84.
    Ren, J., Huo, L., Wang, W., Zhang, Y., Li, W., Lou, J., Xu, T., and Feng, W. (2016) Structural correlation of the neck coil with the coiled-coil (CC1)-forkhead-associated (FHA) tandem for active kinesin-3 KIF13A, J. Biol. Chem., 291, 3581–3594.PubMedCrossRefGoogle Scholar
  85. 85.
    Farkhondeh, A., Niwa, S., Takei, Y., and Hirokawa, N. (2015) Characterizing KIF16B in neurons reveals a novel intramolecular “stalk inhibition” mechanism that regulates its capacity to potentiate the selective somatodendritic localization of early endosomes, J. Neurosci., 35, 5067–5086.PubMedCrossRefGoogle Scholar
  86. 86.
    Yoshimura, Y., Terabayashi, T., and Miki, H. (2010) Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation, Mol. Cell Biol., 30, 2206–2219.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Hsu, C. C., Moncaleano, J. D., and Wagner, O. I. (2011) Subcellular distribution of UNC-104(KIF1A) upon bind-ing to adaptors as UNC-16(JIP3), DNC-1(DCTN1/ Glued) and SYD-2(Liprin-alpha) in C. elegans neurons, Neuroscience, 176, 39–52.PubMedCrossRefGoogle Scholar
  88. 88.
    Wu, G. H., Muthaiyan Shanmugam, M., Bhan, P., Huang, Y. H., and Wagner, O. I. (2016) Identification and characterization of LIN-2(CASK) as a regulator of kinesin-3 UNC-104(KIF1A) motility and clustering in neurons, Traffic, 17, 891–907.PubMedCrossRefGoogle Scholar
  89. 89.
    Tong, Y., Tempel, W., Wang, H., Yamada, K., Shen, L., Senisterra, G. A., Mackenzie, F., Chishti, A. H., and Park, H. W. (2010) Phosphorylation-independent dualsite binding of the FHA domain of KIF13 mediates phospho-inositide transport via centaurin alpha1, Proc. Natl. Acad. Sci. USA, 107, 20346–20351.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Hutagalung, A. H., and Novick, P. J. (2011) Role of Rab GTPases in membrane traffic and cell physiology, Physiol. Rev., 91, 119–149.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Novick, P., and Zerial, M. (1997) The diversity of Rab proteins in vesicle transport, Curr. Opin. Cell Biol., 9, 496–504.PubMedCrossRefGoogle Scholar
  92. 92.
    Zerial, M., and Mcbride, H. (2001) Rab proteins as membrane organizers, Nat. Rev. Mol. Cell Biol., 2, 107–117.PubMedCrossRefGoogle Scholar
  93. 93.
    Fischer Von Mollard, G., Sudhof, T. C., and Jahn, R. (1991) A small GTP-binding protein dissociates from synaptic vesicles during exocytosis, Nature, 349, 79–81.CrossRefGoogle Scholar
  94. 94.
    Stettler, O., Moya, K. L., Zahraoui, A., and Tavitian, B. (1994) Developmental changes in the localization of the synaptic vesicle protein rab3A in rat brain, Neuroscience, 62, 587–600.PubMedCrossRefGoogle Scholar
  95. 95.
    Schluter, O. M., Schmitz, F., Jahn, R., Rosenmund, C., and Sudhof, T. C. (2004) A complete genetic analysis of neuronal Rab3 function, J. Neurosci., 24, 6629–6637.PubMedCrossRefGoogle Scholar
  96. 96.
    Delevoye, C., Miserey-Lenkei, S., Montagnac, G., Gilles-Marsens, F., Paul-Gilloteaux, P., Giordano, F., Waharte, F., Marks, M. S., Goud, B., and Raposo, G. (2014) Recycling endosome tubule morphogenesis from sorting endosomes requires the kinesin motor KIF13A, Cell Rep., 6, 445–454.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Mauvezin, C., Neisch, A. L., Ayala, C. I., Kim, J., Beltrame, A., Braden, C. R., Gardner, M. K., Hays, T. S., and Neufeld, T. P. (2016) Coordination of autophagosome-lysosome fusion and transport by a Klp98A–Rab14 complex in Drosophila, J. Cell Sci., 129, 971–982.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Hallak, M. E., Rodriguez, J. A., Barra, H. S., and Caputto, R. (1977) Release of tyrosine from tyrosinated tubulin. Some common factors that affect this process and the assembly of tubulin, FEBS Lett., 73, 147–150.PubMedCrossRefGoogle Scholar
  99. 99.
    Edde, B., Rossier, J., Le Caer, J. P., Desbruyeres, E., Gros, F., and Denoulet, P. (1990) Posttranslational glutamylation of alpha-tubulin, Science, 247, 83–85.PubMedCrossRefGoogle Scholar
  100. 100.
    Redeker, V., Levilliers, N., Schmitter, J. M., Le Caer, J. P., Rossier, J., Adoutte, A., and Bre, M. H. (1994) Polyglycylation of tubulin: a posttranslational modification in axonemal microtubules, Science, 266, 1688–1691.PubMedCrossRefGoogle Scholar
  101. 101.
    L’hernault, S. W., and Rosenbaum, J. L. (1985) Chlamydomonas alpha-tubulin is posttranslationally modi-fied by acetylation on the epsilon-amino group of a lysine, Biochemistry, 24, 473–478.PubMedCrossRefGoogle Scholar
  102. 102.
    Janke, C. (2014) The tubulin code: molecular compo-nents, readout mechanisms, and functions, J. Cell Biol., 206, 461–472.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Ikegami, K., Heier, R. L., Taruishi, M., Takagi, H., Mukai, M., Shimma, S., Taira, S., Hatanaka, K., Morone, N., Yao, I., Campbell, P. K., Yuasa, S., Janke, C., Macgregor, G. R., and Setou, M. (2007) Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function, Proc. Natl. Acad. Sci. USA, 104, 3213–3218.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    O’hagan, R., Piasecki, B. P., Silva, M., Phirke, P., Nguyen, K. C., Hall, D. H., Swoboda, P., and Barr, M. M. (2011) The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans, Curr. Biol., 21, 1685–1694.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Cai, D., Mcewen, D. P., Martens, J. R., Meyhofer, E., and Verhey, K. J. (2009) Single molecule imaging reveals dif-ferences in microtubule track selection between kinesin motors, PLoS Biol., 7, e1000216.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Seidel, C., Zekert, N., and Fischer, R. (2012) The Aspergillus nidulans kinesin-3 tail is necessary and sufficient to recognize modified microtubules, PLoS One, 7, e30976.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Steinberg, G. (2015) Kinesin-3 in the basidiomycete Ustilago maydis transports organelles along the entire microtubule array, Fungal Genet. Biol., 74, 59–61.PubMedCrossRefGoogle Scholar
  108. 108.
    Bhuwania, R., Castro-Castro, A., and Linder, S. (2014) Microtubule acetylation regulates dynamics of KIF1C-powered vesicles and contact of microtubule plus ends with podosomes, Eur. J. Cell Biol., 93, 424–437.PubMedCrossRefGoogle Scholar
  109. 109.
    Guardia, C. M., Farias, G. G., Jia, R., Pu, J., and Bonifacino, J. S. (2016) BORC functions upstream of kinesins 1 and 3 to coordinate regional movement of lyso-somes along different microtubule tracks, Cell Rep., 17, 1950–1961.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Van Der Vaart, B., Akhmanova, A., and Straube, A. (2009) Regulation of microtubule dynamic instability, Biochem. Soc. Trans., 37, 1007–1013.PubMedCrossRefGoogle Scholar
  111. 111.
    Atherton, J., Houdusse, A., and Moores, C. (2013) MAPping out distribution routes for kinesin couriers, Biol. Cell, 105, 465–487.PubMedGoogle Scholar
  112. 112.
    Schneider, R., Korten, T., Walter Wilhelm, J., and Diez, S. (2015) Kinesin-1 motors can circumvent permanent road-blocks by side-shifting to neighboring protofilaments, Biophys. J., 108, 2249–2257.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Dixit, R., Ross, J. L., Goldman, Y. E., and Holzbaur, E. L. (2008) Differential regulation of dynein and kinesin motor proteins by tau, Science, 319, 1086–1089.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Seitz, A., Kojima, H., Oiwa, K., Mandelkow, E. M., Song, Y. H., and Mandelkow, E. (2002) Single-molecule investi-gation of the interference between kinesin, tau and MAP2c, EMBO J., 21, 4896–4905.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Samora, C. P., Mogessie, B., Conway, L., Ross, J. L., Straube, A., and Mcainsh, A. D. (2011) MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis, Nat. Cell Biol., 13, 1040–1050.PubMedCrossRefGoogle Scholar
  116. 116.
    Semenova, I., Ikeda, K., Resaul, K., Kraikivski, P., Aguiar, M., Gygi, S., Zaliapin, I., Cowan, A., and Rodionov, V. (2014) Regulation of microtubule-based transport by MAP4, Mol. Biol. Cell, 25, 3119–3132.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Lipka, J., Kapitein, L. C., Jaworski, J., and Hoogenraad, C. C. (2016) Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites, EMBO J., 35, 302–318.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Tien, N. W., Wu, G. H., Hsu, C. C., Chang, C. Y., and Wagner, O. I. (2011) Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor’s motility characteristics in C. elegans neurons, Neurobiol. Dis., 43, 495–506.PubMedCrossRefGoogle Scholar
  119. 119.
    Efimova, N., Grimaldi, A., Bachmann, A., Frye, K., Zhu, X., Feoktistov, A., Straube, A., and Kaverina, I. (2014) Podosome-regulating kinesin KIF1C translocates to the cell periphery in a CLASP-dependent manner, J. Cell Sci., 127, 5179–5188.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Kopp, P., Lammers, R., Aepfelbacher, M., Woehlke, G., Rudel, T., Machuy, N., Steffen, W., and Linder, S. (2006) The kinesin KIF1C and microtubule plus ends regulate podosome dynamics in macrophages, Mol. Biol. Cell, 17, 2811–2823.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Ally, S., Larson, A. G., Barlan, K., Rice, S. E., and Gelfand, V. I. (2009) Opposite-polarity motors activate one another to trigger cargo transport in live cells, J. Cell Biol., 187, 1071–1082.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Hancock, W. O. (2014) Bidirectional cargo transport: moving beyond tug of war, Nat. Rev. Mol. Cell Biol., 15, 615–628.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Amrute-Nayak, M., and Bullock, S. L. (2012) Single-molecule assays reveal that RNA localization signals regulate dynein-dynactin copy number on individual transcript cargoes, Nat. Cell Biol., 14, 416–423.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Derr, N. D., Goodman, B. S., Jungmann, R., Leschziner, A. E., Shih, W. M., and Reck-Peterson, S. L. (2012) Tug-of-war in motor protein ensembles revealed with a programmable DNA origami scaffold, Science, 338, 662–665.PubMedCrossRefGoogle Scholar
  125. 125.
    Splinter, D., Tanenbaum, M. E., Lindqvist, A., Jaarsma, D., Flotho, A., Yu, K. L., Grigoriev, I., Engelsma, D., Haasdijk, E. D., Keijzer, N., Demmers, J., Fornerod, M., Melchior, F., Hoogenraad, C. C., Medema, R. H., and Akhmanova, A. (2010) Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate cen-trosome and nuclear positioning during mitotic entry, PLoS Biol., 8, e1000350.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Fu, M. M., and Holzbaur, E. L. (2014) Integrated regulation of motor-driven organelle transport by scaffolding proteins, Trends Cell Biol., 24, 564–574.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Belyy, V., Schlager, M. A., Foster, H., Reimer, A. E., Carter, A. P., and Yildiz, A. (2016) The mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition, Nat. Cell Biol., 18, 1018–1024.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Schlager, M. A., Serra-Marques, A., Grigoriev, I., Gumy, L. F., Esteves Da Silva, M., Wulf, P. S., Akhmanova, A., and Hoogenraad, C. C. (2014) Bicaudal d-family adaptor proteins control the velocity of dynein-based movements, Cell Rep., 8, 1248–1256.PubMedCrossRefGoogle Scholar
  129. 129.
    Kevenaar, J. T., Bianchi, S., Van Spronsen, M., Olieric, N., Lipka, J., Frias, C. P., Mikhaylova, M., Harterink, M., Keijzer, N., Wulf, P. S., Hilbert, M., Kapitein, L. C., De Graaff, E., Ahkmanova, A., Steinmetz, M. O., and Hoogenraad, C. C. (2016) Kinesin-binding protein controls microtubule dynamics and cargo trafficking by regulating kinesin motor activity, Curr. Biol., 26, 849–861.PubMedCrossRefGoogle Scholar
  130. 130.
    Sievers, F., Wilm, A., Dineen, D., Gibson, T. J., Karplus, K., Li, W., Lopez, R., Mcwilliam, H., Remmert, M., Soding, J., Thompson, J. D., and Higgins, D. G. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega, Mol. Syst. Biol., 7,539.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Boc, A., Diallo, A. B., and Makarenkov, V. (2012) T-REX: a web server for inferring, validating and visualizing phylogenetic trees and networks, Nucleic Acids Res., 40, W573–579.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Centre for Mechanochemical Cell BiologyUniversity of WarwickCoventryUK

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