RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly

Brian O. Bodemann, Anthony Orvedahl, Tzuling Cheng, Rosalyn R. Ram, Yi Hung Ou, Etienne Formstecher, Mekhala Maiti, C. Clayton Hazelett, Eric M. Wauson, Maria Balakireva, Jacques H. Camonis, Charles Yeaman, Beth Levine, Michael A. White

Research output: Contribution to journalArticlepeer-review

209 Scopus citations

Abstract

The study of macroautophagy in mammalian cells has described induction, vesicle nucleation, and membrane elongation complexes as key signaling intermediates driving autophagosome biogenesis. How these components are recruited to nascent autophagosomes is poorly understood, and although much is known about signaling mechanisms that restrain autophagy, the nature of positive inductive signals that can promote autophagy remain cryptic. We find that the Ras-like small G protein, RalB, is localized to nascent autophagosomes and is activated on nutrient deprivation. RalB and its effector Exo84 are required for nutrient starvation-induced autophagocytosis, and RalB activation is sufficient to promote autophagosome formation. Through direct binding to Exo84, RalB induces the assembly of catalytically active ULK1 and Beclin1-VPS34 complexes on the exocyst, which are required for isolation membrane formation and maturation. Thus, RalB signaling is a primary adaptive response to nutrient limitation that directly engages autophagocytosis through mobilization of the core vesicle nucleation machinery.

Original languageEnglish (US)
Pages (from-to)253-267
Number of pages15
JournalCell
Volume144
Issue number2
DOIs
StatePublished - Jan 21 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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