Lin Mary Grace, Zhong Qing
Department of Molecular and Cell Biology; University of California, Berkeley; Berkeley, CA USA.
Small GTPases. 2011 Mar;2(2):85-88. doi: 10.4161/sgtp.2.2.15256.
Endocytosis and autophagy are both membrane trafficking pathways vital for cell survival. Endocytosis, the primary means by which cells internalize material such as cell-surface receptors and their protein ligands, is essential for proper cell growth and communication. Autophagy is a catabolic process that degrades cargo ranging from organelles to protein aggregates to bacteria, and it is important for maintaining cellular homeostasis. Defects in both endosome and autophagosome maturation lead to an array of human diseases, including cancer; however, the molecular mechanisms underlying endosome and autophagosome maturation are not well characterized. In the case of endocytosis, small GTPases, key players in membrane organization, are required for endosome maturation. Specifically, activation of the small GTPase Rab7 is required for the initiation of the early-to-late endosome transition, although how this is regulated is largely unknown. Now recent findings from our laboratory show that Rubicon, a component of the PI3KC3 complex, inhibits endosome maturation by preventing activation of Rab7. Not only do our results clarify the molecular link between PI3KC3 and Rab7 function in endosome maturation, they lead us to propose new models for PI3KC3 involvement in membrane trafficking, particularly at the convergence between the endosome and autophagosome pathways.
内吞作用和自噬都是对细胞存活至关重要的膜运输途径。内吞作用是细胞摄取诸如细胞表面受体及其蛋白质配体等物质的主要方式，对细胞的正常生长和通讯至关重要。自噬是一种分解代谢过程，可降解从细胞器到蛋白质聚集体再到细菌等各种物质，对维持细胞内稳态很重要。内体和自噬体成熟过程中的缺陷会导致一系列人类疾病，包括癌症；然而，内体和自噬体成熟的分子机制尚未得到充分表征。就内吞作用而言，小GTP酶是膜组织的关键参与者，是内体成熟所必需的。具体而言，小GTP酶Rab7的激活是早期内体向晚期内体转变起始所必需的，尽管其调控方式在很大程度上尚不清楚。现在我们实验室的最新发现表明，PI3KC3复合物的一个组成部分Rubicon通过阻止Rab7的激活来抑制内体成熟。我们的结果不仅阐明了PI3KC3与Rab7在内体成熟功能之间的分子联系，还促使我们提出PI3KC3参与膜运输的新模型，特别是在内体和自噬体途径的交汇点。
