Cell Division Requires a Direct Link between Microtubule-Bound RacGAP and Anillin in the Contractile Ring

Abstract

The mitotic microtubule array plays two primary roles in cell division. It acts as a scaffold for the congression and separation of chromosomes, and it specifies and maintains the contractile-ring position. The current model for initiation of Drosophila and mammalian cytokinesis [1-5] postulates that equatorial localization of a RhoGEF (Pbl/Ect2) by a microtubule-associated motor protein complex creates a band of activated RhoA [6], which subsequently recruits contractile-ring components such as actin, myosin, and Anillin [1-3]. Equatorial microtubules are essential for continued constriction, but how they interact with the contractile apparatus is unknown. Here, we report the first direct molecular link between the microtubule spindle and the actomyosin contractile ring. We find that the spindle-associated component, RacGAP50C, which specifies the site of cleavage [1-5], interacts directly with Anillin, an actin and myosin binding protein found in the contractile ring [7-10]. Both proteins depend on this interaction for their localization. In the absence of Anillin, the spindle-associated RacGAP loses its association with the equatorial cortex, and cytokinesis fails. These results account for the long-observed dependence of cytokinesis on the continual presence of microtubules at the cortex.

Cytokinesis in Animal Cells

“…Anillin links the plasma membrane with the contractile ring (Liu et al 2012) and recruits the cytoskeletal proteins septins to the cleavage site (Field et al 2005a). It also interacts with ECT2 and RacGAP1, but, unlike CIT-K, loss of anillin does not affect localization of its central spindle partners (D'Avino et al 2008;Gregory et al 2008;Frenette et al 2012). This suggests that these interactions do not play a major structural role, but rather establish a platform necessary to maximize the efficiency of the signaling pathways required for cleavage furrow ingression.…”

Wnt Signaling from Development to Disease: Insights from Model Systems

“…It may act in synergy with Naked cuticle (Nkd). RacGAP50C has a known role in cytokinesis (Gregory et al 2008;Zavortink et al 2005), but its role in Wnt signaling is independent of this, and, surprisingly, independent of GAP activity. The mechanism by which RacGAP50C acts, and whether its mammalian homolog regulates Wnt signaling remain to be determined.…”

Mid1/anillin and the spatial regulation of cytokinesis in fission yeast

“…The fact that the DH domain of Gef2 is necessary for this function also suggests that a Rho GTPase might play a role in this pathway [Ye et al, 2012]. This possibility is especially interesting in light of the fact that in animal cells, anillin serves as a scaffold for the Rho GTPase RhoA and its regulators the RhoGEF Ect2/pebble and RhoGAPMgcRac-GAP/CYK4 during assembly of the contractile ring [D'Avino et al, 2008;Gregory et al, 2008;Piekny and Glotzer, 2008; see also Piekny and Maddox, 2010 for a review; Frenette et al, 2012;Liu et al, 2012;Loria et al, 2012]. Although none of the Rho GTPase family members has been implicated in division plane positioning in fission yeast, it is possible that in this organism, their function has so far been hindered by redundancies in pathways governing contractile ring assembly.…”