Rab2+膜泡介导的高尔基体与自噬小体互作的分子机制

自噬小体是真核细胞自噬过程中形成的一种特有的细胞器，其生成需要其他多种细胞器提供膜组分；而自噬小体则能够识别并包裹多种细胞器，将其运送至溶酶体降解，从而调控其稳态。研究表明，高尔基体在自噬小体生成过程中发挥重要作用，但机制不明；自噬小体能否吞噬高尔基体膜泡及其分子机制尚未知。我们近期研究发现外界胁迫信号经由GM130-Rab2信号轴，从高尔基体向自噬小体传导；自噬小体识别并包裹Rab2标记（Rab2+）的高尔基体膜泡，促进其降解。基于此，我们提出科学假设：高尔基体通过Rab2+膜泡向正在形成的自噬小体输送膜原料；而自噬小体可以吞噬Rab2+膜泡以维持高尔基体的稳态。本项目拟在上述工作的基础上，深入研究Rab2+膜泡介导的高尔基体与自噬小体互作的分子机制，揭示其上游调控信号通路。本研究将阐明高尔基体与自噬小体之间通过相互调控而响应外界刺激的分子机制，相关发现将加深我们对细胞器互作网络的认识。

Autophagosome is a specified organelle which is synthesized during autophagy in eukaryotic cells. Many other organelles contribute to the biogenesis of autophagosomes, and conversely, autophagosome can recognize and enwrap these organelles for their lysosomal degradation, which is crucial for organelle homeostasis. Previous studies have shown that Golgi apparatus plays essential roles in autophagosome formation, however, the mechanisms remain elusive. In addition, it remains unknown whether autophagosome targets Golgi membrane structures for their lysosomal degradation. Our recent work indicates that a GM130-Rab2 signaling axis relay signals from Golgi to autophagosome, and surprisingly, autophagosome may recognize and encapsulate Golgi-derived vesicles to facilitate their degradation. Therefore, we hypothesize that Golgi apparatus donates Rab2+ vesicles to form autophagosome, and that autophagosome targets Golgi-derived Rab2+ vesicles for degradation to maintain the homeostasis of Golgi structure. In this study, we aim to further investigate the molecular mechanism underlying the Golgi-autophagosome interplay, and the upstream signaling pathway. Our work will elucidate a novel mechanism mediating the signal exchange between Golgi and autophagosome, and help to deepen our understanding in inter-organelle interaction network.