B56-PP2A regulates motor dynamics for mitotic chromosome alignment.

Published

Journal Article

Proper alignment of duplicated chromosomes at the metaphase plate involves both motor-driven chromosome movement and the functional and physical end-on connection (K-fiber formation) between the kinetochore and the plus-end of microtubules. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits (B56-PP2A), through their interaction with the mitotic checkpoint protein BUBR1, are required for proper chromosome alignment, but the underlying mechanism(s) has remained elusive. Here, we show that B56-PP2A promotes chromosome alignment primarily by balancing chromosome movement towards the metaphase plate, rather than by directly establishing stable K-fibers. Notably, the poleward movement of chromosomes in cells depleted of the B56 family can be rescued by depletion of HSET (also known as kinesin-14 or KIFC1), a major minus-end-directed motor protein. Strikingly, K-fiber formation can be restored if chromosome movement to the metaphase plate is rescued in B56-depleted cells. Furthermore, the B56-BUBR1 interaction is required for promoting motor-driven chromosome movement towards the metaphase plate. Thus, we propose that B56-PP2A functions in mitotic chromosome alignment by balancing chromosome movement towards the metaphase plate, which is essential for the subsequent establishment of stable and functional kinetochore-microtubule attachments, and mitotic exit.

Full Text

Duke Authors

Cited Authors

  • Xu, P; Virshup, DM; Lee, SH

Published Date

  • November 1, 2014

Published In

Volume / Issue

  • 127 / Pt 21

Start / End Page

  • 4567 - 4573

PubMed ID

  • 25179604

Pubmed Central ID

  • 25179604

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

Digital Object Identifier (DOI)

  • 10.1242/jcs.154609

Language

  • eng

Conference Location

  • England