Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, China.
J Cell Sci. 2012 Apr 1;125(Pt 7):1706-15. doi: 10.1242/jcs.093203. Epub 2012 Feb 10.
Despite recent advances in understanding the functions of autophagy in developmental and pathological conditions, the underlying mechanism of where and how autophagosomal structures acquire membrane remains enigmatic. Here, we provide evidence that post-Golgi membrane traffic plays a crucial role in autophagosome formation. Increased secretion of constitutive cargo from the trans-Golgi network (TGN) to the plasma membrane induced the formation of microtubule-associated protein light chain 3 (LC3)-positive structures. At the early phase of autophagy, LC3 associated with and then budded off from a distinct TGN domain without constitutive TGN-to-plasma cargo and TGN-to-endosome proteins. The clathrin adaptor protein AP1 and clathrin localized to starvation- and rapamycin-induced autophagosomes. Dysfunction of the AP1-dependent clathrin coating at the TGN but not at the plasma membrane prevented autophagosome formation. Our results thus suggest an essential role of the TGN in autophagosome biogenesis, providing membrane to autophagosomes through an AP1-dependent pathway.
尽管近年来在理解自噬在发育和病理条件下的功能方面取得了进展，但自噬体结构在哪里以及如何获得膜的潜在机制仍然是个谜。在这里，我们提供的证据表明，高尔基后膜运输在自噬体形成中起着至关重要的作用。从高尔基网络（TGN）到质膜的组成型货物的分泌增加诱导微管相关蛋白轻链 3（LC3）阳性结构的形成。在自噬的早期阶段，LC3 与一个独特的 TGN 结构域相关联，然后从该结构域中分离出来，而该结构域没有组成型 TGN 到质膜货物和 TGN 到内体蛋白。网格蛋白衔接蛋白 AP1 和网格蛋白定位于饥饿和雷帕霉素诱导的自噬体中。AP1 依赖性网格蛋白包被在 TGN 而非质膜上的功能障碍阻止了自噬体的形成。因此，我们的研究结果表明 TGN 在自噬体生物发生中起着重要作用，通过 AP1 依赖性途径向自噬体提供膜。
