Ramalingam Nagendran, Franke Christof, Jaschinski Evelin, Winterhoff Moritz, Lu Yao, Brühmann Stefan, Junemann Alexander, Meier Helena, Noegel Angelika A, Weber Igor, Zhao Hongxia, Merkel Rudolf, Schleicher Michael, Faix Jan
Anatomy III/Cell Biology, BioMedCenter, Ludwig-Maximilians-University, Grosshaderner Str. 9, Planegg-Martinsried, Germany.
Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
Nat Commun. 2015 Sep 29;6:8496. doi: 10.1038/ncomms9496.
Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. However, how the cortical actin meshwork in the rear is generated remains elusive. Here we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum that generates a subset of filaments as the basis of a resilient cortical actin sheath in the rear. Mechanical resistance of this actin compartment is accomplished by actin crosslinkers and IQGAP-related proteins, and is mandatory to withstand the increased contractile forces in response to mechanical stress by impeding unproductive blebbing in the rear, allowing efficient cell migration in two-dimensional-confined environments. Consistently, ForA supresses the formation of lateral protrusions, rapidly relocalizes to new prospective ends in repolarizing cells and is required for cortical integrity. Finally, we show that ForA utilizes the phosphoinositide gradients in polarized cells for subcellular targeting.
细胞迁移是由较软的前端和较硬的后端皮质特性之间的差异所驱动的，这使得前端能够延伸，而后端能够进行基于肌动球蛋白的收缩。然而，后端的皮质肌动蛋白网络是如何产生的仍然不清楚。在这里，我们从盘基网柄菌中鉴定出类mDia1的formin A（ForA），它产生一部分细丝，作为后端弹性皮质肌动蛋白鞘的基础。这个肌动蛋白区室的机械阻力是由肌动蛋白交联剂和IQGAP相关蛋白完成的，并且通过阻止后端无效的气泡形成来承受因机械应力而增加的收缩力是必不可少的，从而使细胞能够在二维受限环境中高效迁移。一致地，ForA抑制侧向突起的形成，在重新极化的细胞中迅速重新定位到新的预期末端，并且是皮质完整性所必需的。最后，我们表明ForA利用极化细胞中的磷酸肌醇梯度进行亚细胞靶向。
