The 3Ms of central spindle assembly: microtubules, motors and MAPs

Abstract

The central spindle consists of a set of microtubule bundles in anaphase cells that overlap for a short region at their plus ends. The central spindle regulates cleavage furrow formation and completion of cytokinesis. The central spindle forms in anaphase as cells exit mitosis. In unperturbed cells, the central spindle forms from mitotic spindle microtubules. Under appropriate conditions, a bipolar central spindle can form spontaneously from non-spindle microtubules, without a mitotic spindle template. Central spindle microtubule bundles are highly stabilized. The formation of the central spindle requires kinesin motor proteins, microtubule-associated proteins (MAPs) and protein kinases. The central components include centralspindlin (a complex that contains kinesin and Rho GTPase-activating protein subunits), the microtubule-bundling protein protein regulator of cytokinesis 1 (PRC1) and the chromosome passenger complex (CPC). Several of the proteins that are required for central spindle assembly are inactivated by phosphorylation during metaphase, and activated during anaphase. The precise mechanism of microtubule bundling that results in overlapping microtubule plus ends remains be determined. Models of the interactions of motors, MAPs and microtubules provide useful insights into how stable microtubule overlap can be established and suggest that local regulation of microtubule dynamics might have an important role.