Motor domain phosphorylation and regulation of the Drosophila kinesin 13, KLP10A

Vito Mennella, Dong Yan Tan, Daniel W. Buster, Ana B. Asenjo, Uttama Rath, Ao Ma, Hernando J. Sosa, David J. Sharp

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Microtubule (MT)-destabilizing kinesin 13s perform fundamental roles throughout the cell cycle. In this study, we show that the Drosophila melanogaster kinesin 13, KLP10A, is phosphorylated in vivo at a conserved serine (S573) positioned within the α-helix 5 of the motor domain. In vitro, a phosphomimic KLP10A S573E mutant displays a reduced capacity to depolymerize MTs but normal affinity for the MT lattice. In cells, replacement of endogenous KLP10A with KLP10A S573E dampens MT plus end dynamics throughout the cell cycle, whereas a nonphosphorylatable S573A mutant apparently enhances activity during mitosis. Electron microscopy suggests that KLP10A S573 phosphorylation alters its association with the MT lattice, whereas molecular dynamics simulations reveal how KLP10A phosphorylation can alter the kinesin-MT interface without changing important structural features within the motor's core. Finally, we identify casein kinase 1α as a possible candidate for KLP10A phosphorylation. We propose a model in which phosphorylation of the KLP10A motor domain provides a regulatory switch controlling the time and place of MT depolymerization.

Original languageEnglish (US)
Pages (from-to)481-490
Number of pages10
JournalJournal of Cell Biology
Volume186
Issue number4
DOIs
StatePublished - Aug 24 2009

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Microtubules
Phosphorylation
Kinesin
Cell Cycle
Casein Kinase I
Molecular Dynamics Simulation
Drosophila melanogaster
Mitosis
Serine
Drosophila KLP10A protein
Electron Microscopy

ASJC Scopus subject areas

  • Cell Biology

Cite this

Motor domain phosphorylation and regulation of the Drosophila kinesin 13, KLP10A. / Mennella, Vito; Tan, Dong Yan; Buster, Daniel W.; Asenjo, Ana B.; Rath, Uttama; Ma, Ao; Sosa, Hernando J.; Sharp, David J.

In: Journal of Cell Biology, Vol. 186, No. 4, 24.08.2009, p. 481-490.

Research output: Contribution to journalArticle

Mennella, Vito ; Tan, Dong Yan ; Buster, Daniel W. ; Asenjo, Ana B. ; Rath, Uttama ; Ma, Ao ; Sosa, Hernando J. ; Sharp, David J. / Motor domain phosphorylation and regulation of the Drosophila kinesin 13, KLP10A. In: Journal of Cell Biology. 2009 ; Vol. 186, No. 4. pp. 481-490.
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