Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1.
Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1.
复制标题
前缘的内吞膜转换是由Cdc42和Graf1之间的瞬时相互作用驱动的。
DOI：
10.1242/jcs.174417
复制
发表时间：
2015-11-15
影响因子：
4
通讯作者：
Lundmark R
中科院分区：
文献类型：
--
作者：
Francis MK;Holst MR;Vidal-Quadras M;Henriksson S;Santarella-Mellwig R;Sandblad L;Lundmark R
细胞形态的变化需要质膜周转和细胞骨架动力学的协调，这些过程受 Rho GTPases 调节。在这里，我们描述了 Rho GTPase Cdc42 和 GTPase 激活蛋白 (GAP) GRAF1（也称为 ARHGAP26）之间的直接相互作用如何促进前沿细胞表面的快速周转。 Cdc42 和 GRAF1 都是液相摄取所必需的，并调节瞬时 GRAF1 包被的内吞载体的生成，这与网格蛋白包被的囊泡不同。 GRAF1被发现在质膜上离散的富含Cdc42的点处瞬时组装，导致Cdc42的微域关联相应减少。然而，在其活性状态下捕获的 Cdc42 通过 GAP 结构域介导的相互作用，与 GRAF1 一起定位在源自细胞表面的积累的内部结构上。相关荧光和电子断层扫描显微镜显示，这些结构是具有缺陷内体加工的小膜载体簇。我们得出的结论是，Cdc42 和 GRAF1 之间的短暂相互作用驱动内吞周转，并控制通过该机制内化的质膜的内体成熟所必需的转变。摘要：Cdc42 和 GRAF1 之间的短暂相互作用驱动前沿的内吞周转，并控制通过该机制内化的质膜的内体成熟所必需的转变。
Changes in cell morphology require coordination of plasma membrane turnover and cytoskeleton dynamics, processes that are regulated by Rho GTPases. Here, we describe how a direct interaction between the Rho GTPase Cdc42 and the GTPase-activating protein (GAP) GRAF1 (also known as ARHGAP26), facilitates rapid cell surface turnover at the leading edge. Both Cdc42 and GRAF1 were required for fluid-phase uptake and regulated the generation of transient GRAF1-coated endocytic carriers, which were distinct from clathrin-coated vesicles. GRAF1 was found to transiently assemble at discrete Cdc42-enriched punctae at the plasma membrane, resulting in a corresponding decrease in the microdomain association of Cdc42. However, Cdc42 captured in its active state was, through a GAP-domain-mediated interaction, localised together with GRAF1 on accumulated internal structures derived from the cell surface. Correlative fluorescence and electron tomography microscopy revealed that these structures were clusters of small membrane carriers with defective endosomal processing. We conclude that a transient interaction between Cdc42 and GRAF1 drives endocytic turnover and controls the transition essential for endosomal maturation of plasma membrane internalised by this mechanism. Summary: A transient interaction between Cdc42 and GRAF1 drives endocytic turnover at the leading edge, and controls the transition essential for endosomal maturation of plasma membrane internalised by this mechanism.