A novel GDP-bound-Rab27a-interacting protein which regulates endocytosis of insulin secretory membranes

细胞内转运是细胞器间通讯所必需的基本细胞过程。将特定的分子招募到特定的膜位置对于这种贩运是必不可少的。Rab27a是Rab GTPase家族的成员，被认为是胰岛素分泌中胞吐作用的分子开关，在活跃的GTP结合状态和不活跃的GDP结合状态之间循环。我以前曾指出，与GDP结合的Rab27a不是一种不活跃的形式，而实际上是一种活跃的形式，通过GDP依赖的效应元件coronin3来调节内吞作用。在本研究中，我发现GTP结合的CDC42的效应器IQGAP1是Rab27a的另一个GDP依赖的效应器。我的结果表明，CDC42的激活响应于胰岛素促分泌剂葡萄糖，在细胞外围招募内吞机械，包括GDP结合的Rab27a和Coronin3，到IQGAP1，并在该膜位置调节内吞作用。

Intracellular trafficking is a fundamental cellular process that is required for communication between organelles. Recruitment of specific molecules to specific membrane sites is essential for this trafficking. Rab27a, a member of the Rab GTPase family, has been considered to act as a molecular switch for exocytosis in insulin secretion, cycling between an active GTP-bound and an inactive GDP-bound state. I previously showed that GDP-bound Rab27a is not an inactive form but is in fact an active form that regulates endocytosis through the GDP-dependent effector coronin3. In the present study, I identified IQGAP1, an effector of GTP-bound Cdc42, as another GDP-dependent effector of Rab27a. My results indicate that activation of Cdc42 in response to the insulin secretagogue glucose recruits endocytic machinery, including GDP-bound Rab27a and coronin3, to IQGAP1 at the cell periphery and regulates endocytosis at this membrane site.