Frey Yannick, Lungu Cristiana, Meyer Florian, Hauth Franziskus, Hahn Daniel, Kersten Corinna, Heller Vivien, Franz-Wachtel Mirita, Macek Boris, Barsukov Igor, Olayioye Monilola A
University of Stuttgart, Institute of Cell Biology and Immunology, Stuttgart, Germany.
University of Stuttgart, Stuttgart Research Center Systems Biology, Stuttgart, Germany.
iScience. 2024 Jun 6;27(7):110203. doi: 10.1016/j.isci.2024.110203. eCollection 2024 Jul 19.
Deleted in liver cancer 3 (DLC3) is a Rho GTPase-activating protein (RhoGAP) that plays a crucial role in maintaining adherens junction integrity and coordinating polarized vesicle transport by modulating Rho activity at the plasma membrane and endomembranes. By employing bioinformatical sequence analysis, experiments, and assays we here identified a polybasic region (PBR) in DLC3 that facilitates the association of the protein with cellular membranes. Within the PBR, we mapped two serines whose phosphorylation can alter the electrostatic character of the region. Consequently, phosphomimetic mutations of these sites impaired the membrane association of DLC3. Furthermore, we found a new PBR-dependent localization of DLC3 at the midbody region, where the protein locally controlled Rho activity. Here, the phosphorylation-dependent regulation of DLC3 appeared to be required for proper cytokinesis. Our work thus provides a novel mechanism for spatiotemporal termination of Rho signaling by the RhoGAP protein DLC3.
肝癌缺失3（DLC3）是一种Rho GTP酶激活蛋白（RhoGAP），通过调节质膜和内膜上的Rho活性，在维持黏着连接完整性和协调极化囊泡运输中发挥关键作用。通过生物信息序列分析、实验和检测，我们在此鉴定出DLC3中的一个多碱性区域（PBR），该区域促进蛋白质与细胞膜的结合。在PBR内，我们定位了两个丝氨酸，其磷酸化可改变该区域的静电特性。因此，这些位点的磷酸模拟突变损害了DLC3与膜的结合。此外，我们发现DLC3在中体区域有新的PBR依赖性定位，该蛋白在该区域局部控制Rho活性。在这里，DLC3的磷酸化依赖性调节似乎是正确进行胞质分裂所必需的。因此，我们的工作为RhoGAP蛋白DLC3对Rho信号进行时空终止提供了一种新机制。
