AP1 is essential for generation of autophagosomes from the trans-Golgi network
AP1 is essential for generation of autophagosomes from the trans-Golgi network
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AP1 对于跨高尔基体网络产生自噬体至关重要
DOI：
10.1242/jcs.093203
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Guo, Yajuan;Chang, Chunmei;Liu, Wei
尽管最近在理解自噬在发育和病理条件下的功能方面取得了进展，但自噬体结构在何处以及如何获得膜的潜在机制仍然是谜。在这里，我们提供的证据表明，后高尔基体膜交通在自噬体形成中起着至关重要的作用。从trans-Golgi网络（TGN）到质膜的组成性货物分泌增加诱导微管相关蛋白轻链3（LC 3）阳性结构的形成。在自噬的早期阶段，LC 3与不同的TGN结构域相关联，然后从其出芽，而不具有组成性TGN至血浆货物和TGN至内体蛋白。网格蛋白衔接蛋白AP 1和网格蛋白定位于饥饿和雷帕霉素诱导的自噬体。在TGN，但不是在质膜的AP 1依赖网格蛋白涂层功能障碍阻止自噬体的形成。因此，我们的研究结果表明，TGN在自噬体生物合成中起着重要作用，通过AP 1依赖性途径为自噬体提供膜。
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.