Mitotic Motor KIFC1 Is an Organizer of Microtubules in the Axon

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Hemalatha Muralidharan, P W Baas

Abstract

KIFC1 (also called HSET or kinesin-14a) is best known as a multifunctional motor protein essential for mitosis. The present studies are the first to explore KIFC1 in terminally postmitotic 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. 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 cross-links 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 c...Continue Reading

Citations

Oct 20, 2020·Frontiers in Molecular Neuroscience·Laurent GuillaudMarco Terenzio
Jan 16, 2021·Cells·Nadine F JosephSathyanarayanan V Puthanveettil
Apr 3, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Holly V GoodsonSusan H Brawley
Apr 5, 2021·Neuroscience Letters·Shrobona GuhaPeter W Baas
Jul 17, 2021·Frontiers in Cell and Developmental Biology·Alexandra E PetersJessie M Sutherland

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