Microtubule‐actomyosin interactions in cortical flow and cytokinesis

Cytokinesis in animal cells is simultaneously one of the most fascinating and frustrating of cellular phenomena. The fascination stems from its precision and importance, while the frustration stems from its complexity and the wealth of apparently contradictory information about the cellular and molecular mechanisms required for proper cell division [Rappaport, 1996]. Although it is generally accepted that a cortical network of actomyosin provides the force for cell fission, and that microtubules are required for the assembly and positioning of the actomyosin network, the means by which microtubules control the actomyosin cytoskeleton is poorly understood and therefore hotly debated. Cytokinesis can be conceptually divided into three phases: cytokinetic apparatus assembly, furrow progression, and fission completion. Furrow assembly and furrow progression ensue as actomyosin becomes concentrated in the equatorial region as a result of cortical flow, the movement of cortical f-actin, myosin-2, and cell surface proteins [e.g., Wang et al., 1994] toward the site of the forming furrow. Fission completion results when the two daughter cells are completely separated, and may occur minutes to hours after the onset of furrowing. This review is concerned with the first two of these phases and, in particular, the means by which microtubules specify the assembly of the actomyosin apparatus that drives cytokinesis. Two important assumptions underlie the discussion that follows. The first is that furrowing is primarily dependent on paired arrays of microtubules rather than any special feature of the mitotic spindle. This assumption is based on the demonstration that in embryos [Rappaport, 1996], Dictyostelium [Neujahr et al., 1998], and cultured cells [Rieder et al., 1997] furrowing occurs between adjacent asters that lack an intervening spindle. Thus, neither midzone microtubules nor chromosomeassociated microtubules are required for the initiation of furrowing, although midzone microtubules are apparently required for the completion of cytokinesis [e.g., Savoian et al., 1999]. The second assumption is that while cytokinesis is normally entrained to exit from M-phase, the basic microtubule-actomyosin interactions that result in furrow assembly and progression are operative throughout much of the cell cycle. This assumption is based on both the demonstration that cytokinesis can be extended well into interphase by physical [Rappaport, 1996] or pharmacological [Martineau et al., 1995] manipulations, and that cytokinesis occurs in echinoderm embryos locked into M-phase by injection of nondegradable cyclin when the mitotic apparatus is displaced toward the cortex [Shuster and Burgess, 1999]. Thus, in our view, exit fromM-phase is important mainly insofar as it impacts the spatial relationship of microtubules with the cortex. If these assumptions are accepted, then rules established for microtubule-actomyosin interactions in interphase cells