Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D.
Journal of Cell Biology
Rockefeller University Press
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Moreau, K., Ravikumar, B., Puri, C., & Rubinsztein, D. (2012). Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D.. Journal of Cell Biology, 196 (4), 483-496. https://doi.org/10.1083/jcb.201110114
Macroautophagy (in this paper referred to as autophagy) and the ubiquitin-proteasome system are the two major catabolic systems in cells. Autophagy involves sequestration of cytosolic contents in double membrane-bounded vesicles called autophagosomes. The membrane source for autophagosomes has received much attention, and diverse sources, such as the plasma membrane, Golgi, endoplasmic reticulum, and mitochondria, have been implicated. These may not be mutually exclusive, but the exact sources and mechanism involved in the formation of autophagosomes are still unclear. In this paper, we identify a positive role for the small G protein Arf6 in autophagosome formation. The effect of Arf6 on autophagy is mediated by its role in the generation of phosphatidylinositol 4,5-bisphosphate (PIP(2)) and in inducing phospholipase D (PLD) activity. PIP(2) and PLD may themselves promote autophagosome biogenesis by influencing endocytic uptake of plasma membrane into autophagosome precursors. However, Arf6 may also influence autophagy by indirect effects, such as either by regulating membrane flow from other compartments or by modulating PLD activity independently of the mammalian target of rapamycin.
ADP-Ribosylation Factors, Animals, Autophagy, Autophagy-Related Proteins, Blotting, Western, CHO Cells, Carrier Proteins, Cell Membrane, Cricetinae, Endocytosis, Endoplasmic Reticulum, Fluorescent Antibody Technique, GTPase-Activating Proteins, Golgi Apparatus, Green Fluorescent Proteins, HeLa Cells, Humans, Immunosuppressive Agents, Phagosomes, Phosphatidylinositol 4,5-Diphosphate, Phospholipase D, Sirolimus, TOR Serine-Threonine Kinases
We are grateful for funding from a Wellcome Trust Senior and Principal Research Fellowships (to D.C. Rubinsztein) and Cancer Research UK (to C. Puri).
Wellcome Trust (095317/Z/11/A)
Wellcome Trust (095317/Z/11/Z)
External DOI: https://doi.org/10.1083/jcb.201110114
This record's URL: https://www.repository.cam.ac.uk/handle/1810/295384
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Licence URL: https://creativecommons.org/licenses/by-nc-sa/4.0/