Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117597, Singapore.
Cell Mol Life Sci. 2011 Oct;68(20):3349-58. doi: 10.1007/s00018-011-0748-9. Epub 2011 Jun 18.
Macroautophagy, the process by which cytosolic components and organelles are engulfed and degraded by a double-membrane structure, could be viewed as a specialized, multistep membrane transport process. As such, it intersects with the exocytic and endocytic membrane trafficking pathways. A number of Rab GTPases which regulate secretory and endocytic membrane traffic have been shown to play either critical or accessory roles in autophagy. The biogenesis of the pre-autophagosomal isolation membrane (or phagophore) is dependent on the functionality of Rab1. A non-canonical, Atg5/Atg7-independent mode of autophagosome generation from the trans-Golgi or endosome requires Rab9. Other Rabs, such as Rab5, Rab24, Rab33, and Rab7 have all been shown to be required, or involved at various stages of autophagosomal genesis and maturation. Another small GTPase, RalB, was very recently demonstrated to induce isolation membrane formation and maturation via its engagement of the exocyst complex, a known Rab effector. We summarize here what is now known about the involvement of Rabs in autophagy, and discuss plausible mechanisms with future perspectives.
巨自噬是一种将细胞质成分和细胞器包裹并降解的双层膜结构的过程，可以被视为一种特殊的、多步骤的膜运输过程。因此，它与胞吐和胞吞膜运输途径相交。已经证明，许多调节分泌和胞吞膜运输的 Rab GTPases 在自噬中发挥关键或辅助作用。前自噬体隔离膜（或噬泡）的生物发生依赖于 Rab1 的功能。从高尔基复合体或内体产生非典型的、Atg5/Atg7 非依赖性自噬体的方式需要 Rab9。其他 Rab 蛋白，如 Rab5、Rab24、Rab33 和 Rab7，都被证明是必需的，或者在自噬体发生和成熟的各个阶段都有参与。另一种小 GTPase，RalB，最近被证明通过其与外核复合物的结合来诱导隔离膜的形成和成熟，外核复合物是一种已知的 Rab 效应物。在这里，我们总结了现在已知的 Rab 参与自噬的情况，并讨论了未来的可能机制和前景。
