The plasma membrane as a control center for autophagy |
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Authors: | Moreau Kevin Rubinsztein David C |
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Institution: | Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Cambridge, UK. |
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Abstract: | Autophagosomes may derive membrane from diverse sources, including the plasma membrane, Golgi, endoplasmic reticulum and mitochondria. The plasma membrane contributes membrane to ATG12-ATG5-ATG16L1-positive phagophore precursor vesicles (LC3-negative) by both clathrin-dependent and -independent routes. We recently observed that ARF6 regulates autophagy and that this could be explained, at least in part, by its role in the generation of phosphatidylinositol 4,5-bisphosphate PtdIns(4,5)P 2], which influences endocytic uptake of plasma membrane into autophagosome precursors. The subsequent maturation of these small phagophore precursors into phagophores (ATG12-ATG5-ATG16L1-positive and LC3-positive), is assisted by SNARE-mediated homotypic fusion that increase their size and enhance their ability to acquire LC3-II. It appears that a plasma membrane-derived pool of VAMP7 is a key mediator of these fusion events. Thus, events at the plasma membrane may regulate distinct steps in the biogenesis of phagophores. |
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Keywords: | Arf6 ATG16L1 autophagy phagophore plasma membrane SNARE |
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