Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity

Xin Zhang1, Stephanie C Ems-McClung, Claire E Walczak

  • 1Departments of Biochemistry and Molecular Biology, and Medical Sciences, Indiana University, Bloomington, IN 47405, USA.

Insights

Mitotic centromere-associated kinesin (MCAK) regulation by Aurora A is crucial for spindle formation. Aurora A controls MCAK

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitotic centromere-associated kinesin (MCAK) plays roles in mitosis.
  • MCAK localization and activity at chromatin/kinetochores are regulated by Aurora B kinase.
  • Regulation of cytoplasmic and spindle pole-localized MCAK is not well understood.

Purpose of the Study:

  • To investigate the regulation of MCAK by Aurora A kinase.
  • To understand MCAK's role in microtubule organization and spindle formation in the absence of chromatin and centrosomes.

Main Methods:

  • Utilized Xenopus egg extracts to assemble spindles without chromatin or centrosomes.
  • Investigated MCAK localization and activity using immunofluorescence and biochemical assays.
  • Analyzed the role of specific Aurora A phosphorylation sites (S196 and S719) on MCAK function.

Main Results:

  • MCAK localization and activity are regulated by Aurora A in Xenopus egg extracts.
  • Aurora A-dependent phosphorylation of MCAK at S196 regulates pole focusing at aster centers.
  • Phosphorylation at S719 by Aurora A enhances bipolar spindle formation.
  • MCAK colocalizes with NuMA and XMAP215 at the center of Ran asters.

Conclusions:

  • Aurora A plays a key role in regulating MCAK localization and activity during spindle assembly.
  • MCAK phosphorylation by Aurora A at S196 and S719 contributes to proper pole focusing and bipolar spindle formation.
  • This study identifies novel roles for MCAK at spindle poles and highlights Aurora A as a key regulator of spindle bipolarity.

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