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Involvement of members of the Rab family and related small GTPases in autophagosome formation and maturation

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Abstract

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.

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Acknowledgements

Rab-associated work in BLT’s laboratory was supported by a grant from the Biomedical Research Council (08/1/21/19/533). SNARE-associated work was funded by an AcRF tier 1 grant from the Ministry of Education of Singapore (Project no. T13-0802-P13). CEC is a recipient of the NUS Graduate School of Integrative Sciences and Engineering (NGS) scholarship. The authors declare no financial conflicts of interest.

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  1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 8 Medical Drive, Singapore, 117597, Singapore

    Christelle En Lin Chua, Bin Qi Gan & Bor Luen Tang

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  1. Christelle En Lin Chua
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Chua, C.E.L., Gan, B.Q. & Tang, B.L. Involvement of members of the Rab family and related small GTPases in autophagosome formation and maturation. Cell. Mol. Life Sci. 68, 3349–3358 (2011). https://doi.org/10.1007/s00018-011-0748-9

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