Positioning the Plane of Cell Division during Cytokinesis

描述（由申请人提供）：成功的细胞分裂需要对细胞骨架进行精确的时空控制，以便在分离的姐妹染色单体之间形成进入的分裂沟。收缩环组装发生在细胞皮层，细胞质区与质膜并列。这个过程的主要调节因子，小的GTPase RhoA，在赤道细胞皮层被激活的机制并不清楚

DESCRIPTION (provided by applicant): Successful cell division requires exquisite spatial and temporal control of the cytoskeleton such that the ingressing cleavage furrow forms between the separating sisters chromatids. Contractile ring assembly occurs in the cell cortex, the cytoplasmic region juxtaposed to the plasma membrane. The mechanism by which the master regulator of this process, the small GTPase RhoA, is activated at the equatorial cell cortex is not well understood. New evidence has been obtained that reveals a previously unidentified inhibitory mechanism. Preliminary results suggest that characterization of this inhibitory mechanism will provide insights into how exchange factors promote RhoA activation. These results and evidence from a variety of systems suggest a hypothesis in which plasma membrane targeting of guanine nucleotide exchange factors is a key step in activating GTPase pathways and that, once active, the primary function that GTPases serve is to recruit effectors to the appropriate membrane environment. This hypothesis will be directly tested in the context of cytokinesis using recently developed optogenetic tools that affords control of protein localization and function in living cells using light. Lastly, experiments will be performed to uncover the molecular function of a novel GYF-domain containing protein that regulates RhoA-dependent cortical contractility.