A model for the regulatory network controlling the dynamics of kinetochore microtubule plus-ends and poleward flux in metaphase

Nicolas Fernandez, Qiang Chang, Daniel W. Buster, David J. Sharp, Ao Ma

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Tight regulation of kinetochore microtubule dynamics is required to generate the appropriate position and movement of chromosomes on the mitotic spindle. A widely studied but mysterious aspect of this regulation occurs during metaphase when polymerization of kinetochore microtubule plus-ends is balanced by depolymerization at their minus-ends. Thus, kinetochore microtubules maintain a constant net length, allowing chromosomes to persist at the spindle equator, but consist of tubulin subunits that continually flux toward spindle poles. Here, we construct a feasible network of regulatory proteins for controlling kinetochore microtubule plus-end dynamics, which was combined with a Monte Carlo algorithm to simulate metaphase tubulin flux. We also test the network model by combining it with a force-balancing model explicitly taking force generators into account. Our data reveal how relatively simple interrelationships among proteins that stimulate microtubule plus-end polymerization, depolymerization, and dynamicity can induce robust flux while accurately predicting apparently contradictory results of knockdown experiments. The model also provides a simple and robust physical mechanism through which the regulatory networks at kinetochore microtubule plus- and minus-ends could communicate.

Original languageEnglish (US)
Pages (from-to)7846-7851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number19
DOIs
StatePublished - May 12 2009

Keywords

  • Kinesin
  • Mitosis

ASJC Scopus subject areas

  • General

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