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

细胞内运输是细胞器间通讯所必需的基本细胞过程。将特定分子招募到特定的膜位点对这种运输至关重要。Rab27a是rabgtpase家族的一员，被认为是胰岛素分泌过程中胞外分泌的分子开关，在活跃的gtp结合状态和不活跃的gdp结合状态之间循环。我之前表明，gdp结合的Rab27a不是无活性形式，而是实际上是一种活性形式，通过gdp依赖性效应物coronin3调节内吞噬作用。在本研究中，我发现gtp结合Cdc42的效应物IQGAP1是Rab27a的另一个gdp依赖性效应物。我的研究结果表明，Cdc42在胰岛素促分泌物葡萄糖的激活下，将胞吞机制，包括gdp结合的Rab27a和coronin3，招募到细胞周围的IQGAP1，并调节该膜部位的胞吞作用。

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.