CLIC4, a new component of the cytokinetic ring, regulates actin cytoskeleton dynamics during the anaphase-to-telophase transition

During mitotic cell division, the actin cytoskeleton undergoes several dynamic changes that lead to cell rounding during metaphase, the formation and ingression of the cytokinetic contractile ring during anaphase, and finally the formation of the intercellular bridge during telophase. These dramatic changes in the organization of the actomyosin cytoskeleton play a key role in progression through mitosis and are regulated by a number of proteins. While the regulators of cytokinetic ring formation and contraction are well-established, very little is known about the proteins that are responsible for the changing actin dynamics during the transition from an actively ingressing cytokinetic furrow to the stable intercellular bridge connecting two daughter cells during telophase. Here, we describe a role for CLIC4 in regulating this anaphase-to-telophase transition. We first describe CLIC4 as a new component of the cytokinetic ring that is required for successful completion of mitotic cell division. We also show that RhoA recruits CLIC4 to the cytokinetic ring and that CLIC4regulates the formation of a stable intercellular bridge by preventing regression of the cytokinetic furrow. Finally, we demonstrate that CLIC4 regulates the remodeling of sub-plasma membrane actomyosin network within the furrow by recruiting MST4 kinase and regulating ezrin phosphorylation. This work identifies and characterizes new molecular players involved in the transition from the contracting cytokinetic ring to the intercellular bridge during cytokinesis.