Sci. Signal., 25 January 2011
Autophagy Rallying the Troops
John F. Foley
Science Signaling, AAAS, Washington, DC 20005, USA
When a cell experiences nutrient deprivation, it triggers macroautophagy, a process by which certain of its cytoplasmic contents are enclosed in an autophagosome, a double-membraned vesicle. Fusion of autophagosomes with lysosomes results in degradation of the enclosed cargo so that the cell can use the raw materials to survive. Autophagosome formation involves multiple steps and is mediated by protein complexes that drive vesicle nucleation and membrane elongation until the targeted components are cut off from the rest of the cytoplasm (see commentary by Farré and Subramani). Noting that autophagy plays a role in the immune response to pathogens, which also involves some components of the exocyst, a heterooctomeric complex that regulates vesicular traffic to the plasma membrane, Bodemann et al. investigated interactions between exocyst components and autophagy proteins. They found a number of interactions, including interactions between the exocyst component Exo84 and some components of the autophagy machinery. Assembly of the exocyst depends on the activities of the Ras-like GTPases RalA and RalB. Depletion of RalB, but not RalA, blocked the induction of autophagy by nutrient starvation, whereas overexpression of a constitutively active mutant form of RalB in cells in nutrient-rich conditions was sufficient to induce autophagy. Nutrient starvation triggered the physical association of Exo84, RalB, and Beclin1, a central inducer of autophagy. The resulting recruitment of additional components led to the formation of an active autophagy initiation complex. Together, these data suggest that RalB is activated in response to nutrient deprivation and triggers assembly of the autophagy machinery on the platform provided by the exocyst.
B. O. Bodemann, A. Orvedahl, T. Cheng, R. R. Ram, Y.-H. Ou, E. Formstecher, M. Maiti, C. C. Hazelett, E. M. Wauson, M. Balakireva, J. H. Camonis, C. Yeaman, B. Levine, M. A. White, RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell 144, 253–267 (2011). [PubMed]
J.-C. Farré, S. Subramani, Rallying the exocyst as an autophagy scaffold. Cell 144, 172–174 (2011). [PubMed]
Citation: J. F. Foley, Rallying the Troops. Sci. Signal. 4, ec26 (2011).
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