Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation

Lesley N. Weaver, Stephanie C. Ems-McClung, Jane R. Stout, Chantal Leblanc, Sidney L. Shaw, Melissa K. Gardner, Claire Walczak

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The mitotic spindle is a macromolecular structure utilized to properly align and segregate sister chromatids to two daughter cells. During mitosis, the spindle maintains a constant length, even though the spindle microtubules (MTs) are constantly undergoing polymerization and depolymerization [1]. Members of the kinesin-8 family are important for the regulation of spindle length and for chromosome positioning [2-9]. Kinesin-8 proteins are length-specific, plus-end-directed motors that are proposed to be either MT depolymerases [3, 4, 8, 10, 11] or MT capping proteins [12]. How Kif18A uses its destabilization activity to control spindle morphology is not known. We found that Kif18A controls spindle length independently of its role in chromosome positioning. The ability of Kif18A to control spindle length is mediated by an ATP-independent MT binding site at the C-terminal end of the Kif18A tail that has a strong affinity for MTs in vitro and in cells. We used computational modeling to ask how modulating the motility or binding properties of Kif18A would affect its activity. Our modeling predicts that both fast motility and a low off rate from the MT end are important for Kif18A function. In addition, our studies provide new insight into how depolymerizing and capping enzymes can lead to MT destabilization.

Original languageEnglish
Pages (from-to)1500-1506
Number of pages7
JournalCurrent Biology
Volume21
Issue number17
DOIs
StatePublished - Sep 13 2011

Fingerprint

Microtubules
microtubules
binding sites
Kinesin
tail
Binding Sites
Chromosomes
Chromosome Positioning
Depolymerization
kinesin
Proteins
Adenosine Triphosphate
Polymerization
Microtubule Proteins
Spindle Apparatus
Chromatids
Chromosomes, Human, Pair 2
chromosomes
Enzymes
mitotic spindle apparatus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Weaver, L. N., Ems-McClung, S. C., Stout, J. R., Leblanc, C., Shaw, S. L., Gardner, M. K., & Walczak, C. (2011). Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation. Current Biology, 21(17), 1500-1506. https://doi.org/10.1016/j.cub.2011.08.005

Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation. / Weaver, Lesley N.; Ems-McClung, Stephanie C.; Stout, Jane R.; Leblanc, Chantal; Shaw, Sidney L.; Gardner, Melissa K.; Walczak, Claire.

In: Current Biology, Vol. 21, No. 17, 13.09.2011, p. 1500-1506.

Research output: Contribution to journalArticle

Weaver, LN, Ems-McClung, SC, Stout, JR, Leblanc, C, Shaw, SL, Gardner, MK & Walczak, C 2011, 'Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation', Current Biology, vol. 21, no. 17, pp. 1500-1506. https://doi.org/10.1016/j.cub.2011.08.005
Weaver LN, Ems-McClung SC, Stout JR, Leblanc C, Shaw SL, Gardner MK et al. Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation. Current Biology. 2011 Sep 13;21(17):1500-1506. https://doi.org/10.1016/j.cub.2011.08.005
Weaver, Lesley N. ; Ems-McClung, Stephanie C. ; Stout, Jane R. ; Leblanc, Chantal ; Shaw, Sidney L. ; Gardner, Melissa K. ; Walczak, Claire. / Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation. In: Current Biology. 2011 ; Vol. 21, No. 17. pp. 1500-1506.
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