Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching.
Kinesin-12 (also called Kif15) is a mitotic motor protein that continues to be expressed in developing neurons. Depletion of kinesin-12 causes axons to grow faster, more than doubles the frequency of microtubule transport in both directions in the axon, prevents growth cones from turning properly, and enhances the invasion of microtubules into filopodia. These results are remarkably similar to those obtained in previous studies in which neurons were depleted of kinesin-5 (also called Eg5 or Kif11), another mitotic motor protein that continues to be expressed in developing neurons. However, there are also notable differences in the phenotypes obtained with depleting each of these motors. Depleting kinesin-12 decreases axonal branching and growth cone size, whereas inhibiting kinesin-5 increases these parameters. In addition, depleting kinesin-12 diminishes the appearance of growth-cone-like waves along the length of the axon, an effect not observed with depletion of kinesin-5. Finally, depletion of kinesin-12 abolishes the "waggling" behavior of microtubules that occurs as they assemble along actin bundles within filopodia, whereas inhibition of kinesin-5 does not. Interestingly, and perhaps relevant to these differences in phenotype, in biochemical studies, kinesin-12 coimmunoprecipitates with actin but kinesin-5 does not. Collectively, these findings support a scenario whereby kinesin-12 shares functions with kinesin-5 related to microtubule-microtubule interactions, but kinesin-12 has other functions not shared by kinesin-5 that are related to the ability of kinesin-12 to interact with actin.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Mei
M
Liu
Vidya C
VC
Nadar
Frank
F
Kozielski
Marta
M
Kozlowska
Wenqian
W
Yu
Peter W
PW
Baas
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D016547:Kinesins / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D055495:Neurogenesis / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats
C521566:KIF5B protein, rat; C481488:Kif15 protein, rat; D008869:Microtubule-Associated Proteins; C547919:Kif5A protein, rat; D016547:Kinesins