Rho signalling in cytokinesis

Abstract

We have carried out a genetic screen in Drosophila for genes that drive the final stage of cell division, cytokinesis. The small GTPase Rho is a key signalling molecule that must be activated to initiate cell cleavage, so our screen was designed to identify genes that mediate Rho signalling to bring about cell division. We have identified a set of genes which, when overexpressed can compensate for reduced Rho signalling, and are in the process of elucidating their role in cytokinesis. Our first candidate gene from the screen was Citron kinase, which we have shown localising to the cleavage furrow in living cells, and which requires active Rho to do so.Wehave also shown that Citron physically interacts with Rho, and is found in proliferating cells during development. Genetic interactions indicate that Citron is specifically required for Rho signal transduction in cytokinesis, and consistent with that, we have demonstrated a failure of cytokinesis in Citron mutant cells. Vertebrate cell culture work has suggested that Citron might be necessary for the phosphorylation of myosin, however we have shown that clear loss of Citron and failure of cytokinesis takes place without a reduction in myosin phosphorylation, indicating that the essential target for Citron is still to be found.Wehave addressed the issue of what Rho effector might then be regulating myosin, and the evidence so far suggests that neither Rho kinase, Myosin Light Chain kinase nor Citron are essential by themselves.