Kinesin-12, a Mitotic Microtubule-Associated Motor Protein, Impacts Axonal Growth, Navigation, and Branching
Open Access
- 3 November 2010
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 30 (44), 14896-14906
- https://doi.org/10.1523/jneurosci.3739-10.2010
Abstract
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.This publication has 44 references indexed in Scilit:
- Kinesin-1 heavy chain mediates microtubule sliding to drive changes in cell shapeProceedings of the National Academy of Sciences of the United States of America, 2010
- Mitotic functions of kinesin-5Seminars in Cell & Developmental Biology, 2010
- The Role of Hklp2 in the Stabilization and Maintenance of Spindle BipolarityCurrent Biology, 2009
- Kif15 Cooperates with Eg5 to Promote Bipolar Spindle AssemblyCurrent Biology, 2009
- Growth cone‐like waves transport actin and promote axonogenesis and neurite branchingDevelopmental Neurobiology, 2009
- Kinesin‐5 in Drosophila embryo mitosis: Sliding filament or spindle matrix mechanism?Cell Motility, 2009
- Kinesin-5 Is Essential for Growth-Cone TurningCurrent Biology, 2008
- Mechanisms of Mitotic Spindle Assembly and FunctionInternational Review of Cytology, 2008
- Microtubules and Neuronal Polarity: Lessons from MitosisNeuron, 1999
- A bipolar kinesinNature, 1996