MCAK activity at microtubule tips regulates spindle microtubule length to promote robust kinetochore attachment

J Cell Biol. 2012 Apr 16;197(2):231-7. doi: 10.1083/jcb.201108147. Epub 2012 Apr 9.

Abstract

Mitotic centromere-associated kinesin (MCAK) is a microtubule-depolymerizing kinesin-13 member that can track with polymerizing microtubule tips (hereafter referred to as tip tracking) during both interphase and mitosis. MCAK tracks with microtubule tips by binding to end-binding proteins (EBs) through the microtubule tip localization signal SKIP, which lies N terminal to MCAK's neck and motor domain. The functional significance of MCAK's tip-tracking behavior during mitosis has never been explained. In this paper, we identify and define a mitotic function specific to the microtubule tip-associated population of MCAK: negative regulation of microtubule length within the assembling bipolar spindle. This function depends on MCAK's ability to bind EBs and track with polymerizing nonkinetochore microtubule tips. Although this activity antagonizes centrosome separation during bipolarization, it ultimately benefits the dividing cell by promoting robust kinetochore attachments to the spindle microtubules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle Proteins / metabolism
  • Centromere / metabolism
  • Centrosome / metabolism
  • HeLa Cells
  • Humans
  • Kinesin / antagonists & inhibitors
  • Kinesin / genetics*
  • Kinesin / metabolism*
  • Kinetochores / metabolism*
  • Microtubules / physiology*
  • Mitosis
  • Nuclear Proteins / metabolism
  • Phosphoric Monoester Hydrolases / metabolism
  • Pyrimidines / pharmacology
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction / genetics
  • Spindle Apparatus / physiology*
  • Spindle Apparatus / ultrastructure
  • Thiones / pharmacology

Substances

  • Cell Cycle Proteins
  • KIF11 protein, human
  • KIF2C protein, human
  • MAD1L1 protein, human
  • Nuclear Proteins
  • Pyrimidines
  • RNA, Small Interfering
  • Thiones
  • monastrol
  • SKIP enzyme, human
  • Phosphoric Monoester Hydrolases
  • Kinesin