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Mitotic Motor KIFC1 is an organizer of microtubules in the axon.
Journal of Neuroscience 2019 Februrary 26
KIFC1 (also called HSET or kinesin-14a) is best known as a multi-functional motor protein essential for mitosis. The present studies are the first to explore KIFC1 in terminally post-mitotic neurons. Using RNA interference to partially deplete KIFC1 from rat neurons (from animals of either gender) in culture, pharmacologic agents that inhibit KIFC1, and expression of mutant KIFC1 constructs, we demonstrate critical roles for KIFC1 in regulating axonal growth and retraction as well as growth cone morphology. Experimental manipulations of KIFC1 elicit morphological changes in the axon as well as changes in the organization, distribution and polarity orientation of its microtubules. Taken together, the results indicate a mechanism by which KIFC1 binds to microtubules in the axon and slides them into alignment in an ATP-dependent fashion and then crosslinks them in an ATP-independent fashion to oppose their subsequent sliding by other motors. SIGNIFICANCE STATEMENT Here we establish that KIFC1, a molecular motor well characterized in mitosis, is robustly expressed in neurons, where it has profound influence on the organization of microtubules in a number of different functional contexts. KIFC1 may help answer long-standing questions in cellular neuroscience such as, mechanistically, how growth cones stall and how axonal microtubules resist forces that would otherwise cause the axon to retract. Knowledge about KIFC1 may help researchers to devise strategies for treating disorders of the nervous system involving axonal retraction, given that KIFC1 is expressed in adult neurons as well as developing neurons.
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