An agent-based model contrasts opposite effects of dynamic and stable microtubules on cleavage furrow positioning

Authored by Garrett M. Odell, Victoria E. Foe

Date Published: 2008-11-03

DOI: 10.1083/jcb.200807129

Sponsors: No sponsors listed

Platforms: Java

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

From experiments by Foe and von Dassow (Foe, V. E., and G. von Dassow. 2008. J. Cell Biol. 183: 457-470) and others, we infer a molecular mechanism for positioning the cleavage furrow during cytokinesis. Computer simulations reveal how this mechanism depends on quantitative motor-behavior details and explore how robustly this mechanism succeeds across a range of cell sizes. The mechanism involves the MKLP1 (kinesin-6) component of centralspindlin binding to and walking along microtubules to stimulate cortical contractility where the centralspindlin complex concentrates. The majority of astral microtubules are dynamically unstable. They bind most MKLP1 and suppress cortical Rho/myosin II activation because the tips of unstable microtubules usually depolymerize before MKLP1s reach the cortex. A subset of astral microtubules stabilizes during anaphase, becoming effective rails along which MKLP1 can actually reach the cortex. Because stabilized microtubules aim statistically at the equatorial spindle midplane, that is where centralspindlin accumulates to stimulate furrow formation.

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