Journal article
RalB and the Exocyst Mediate the Cellular Starvation Response by Direct Activation of Autophagosome Assembly
Cell (Cambridge), Vol.144(2), pp.253-267
2011
DOI: 10.1016/j.cell.2010.12.018
PMCID: PMC3038590
PMID: 21241894
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.
Details
- Title: Subtitle
- RalB and the Exocyst Mediate the Cellular Starvation Response by Direct Activation of Autophagosome Assembly
- Creators
- Brian O Bodemann - Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USAAnthony Orvedahl - Department of Internal Medicine and Microbiology and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-9039, USATzuling Cheng - Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USARosalyn R Ram - Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USAYi-Hung Ou - Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USAEtienne Formstecher - Hybrigenics, Inc., 75014 Paris, FranceMekhala Maiti - Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USAC. Clayton Hazelett - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USAEric M Wauson - Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USAMaria Balakireva - Institut Curie, Inserm U-548, 75248 Paris, FranceJacques H Camonis - Institut Curie, Inserm U-548, 75248 Paris, FranceCharles Yeaman - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USABeth Levine - Department of Internal Medicine and Microbiology and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-9039, USAMichael A White - Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.144(2), pp.253-267
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2010.12.018
- PMID
- 21241894
- PMCID
- PMC3038590
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2011
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025465702771
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