4.7 Article

Drosophila kinesin-8 stabilizes the kinetochore-microtubule interaction

期刊

JOURNAL OF CELL BIOLOGY
卷 218, 期 2, 页码 474-488

出版社

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201807077

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资金

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [15KT0077, 17H01431]
  2. Laura and Arthur Colwin Endowed Summer Research Fellowship Fund (2015) of the Marine Biological Laboratory
  3. JSPS [16J02807]
  4. Grants-in-Aid for Scientific Research [16J02807, 15KT0077, 17H01431] Funding Source: KAKEN

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Kinesin-8 is required for proper chromosome alignment in a variety of animal and yeast cell types. However, it is unclear how this motor protein family controls chromosome alignment, as multiple biochemical activities, including inconsistent ones between studies, have been identified. Here, we find that Drosophila kinesin-8 (Klp67A) possesses both microtubule (MT) plus end-stabilizing and -destabilizing activity, in addition to kinesin-8's commonly observed MT plus end-directed motility and tubulin-binding activity in vitro. We further show that Klp67A is required for stable kinetochore-MT attachment during prometaphase in S2 cells. In the absence of Klp67A, abnormally long MTs interact in an end-on fashion with kinetochores at normal frequency. However, the interaction is unstable, and MTs frequently become detached. This phenotype is rescued by ectopic expression of the MT plus end-stabilizing factor CLASP, but not by artificial shortening of MTs. We show that human kinesin-8 (KIF18A) is also important to ensure proper MT attachment. Overall, these results suggest that the MT-stabilizing activity of kinesin-8 is critical for stable kinetochore-MT attachment.

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