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 journalArticle

194 Citations (Scopus)

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

Fingerprint

Autophagy
Starvation
Nutrients
Chemical activation
Nucleation
Membranes
Monomeric GTP-Binding Proteins
Food
Machinery
Elongation
Cells
Autophagosomes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. / Bodemann, Brian O.; Orvedahl, Anthony; Cheng, Tzuling; Ram, Rosalyn R.; Ou, Yi Hung; Formstecher, Etienne; Maiti, Mekhala; Hazelett, C. Clayton; Wauson, Eric M.; Balakireva, Maria; Camonis, Jacques H.; Yeaman, Charles; Levine, Beth; White, Michael A.

In: Cell, Vol. 144, No. 2, 21.01.2011, p. 253-267.

Research output: Contribution to journalArticle

Bodemann, BO, Orvedahl, A, Cheng, T, Ram, RR, Ou, YH, Formstecher, E, Maiti, M, Hazelett, CC, Wauson, EM, Balakireva, M, Camonis, JH, Yeaman, C, Levine, B & White, MA 2011, 'RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly', Cell, vol. 144, no. 2, pp. 253-267. https://doi.org/10.1016/j.cell.2010.12.018
Bodemann, Brian O. ; Orvedahl, Anthony ; Cheng, Tzuling ; Ram, Rosalyn R. ; Ou, Yi Hung ; Formstecher, Etienne ; Maiti, Mekhala ; Hazelett, C. Clayton ; Wauson, Eric M. ; Balakireva, Maria ; Camonis, Jacques H. ; Yeaman, Charles ; Levine, Beth ; White, Michael A. / RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. In: Cell. 2011 ; Vol. 144, No. 2. pp. 253-267.
@article{5d898bbd27604f30a2dab9a000a05b88,
title = "RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly",
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.",
author = "Bodemann, {Brian O.} and Anthony Orvedahl and Tzuling Cheng and Ram, {Rosalyn R.} and Ou, {Yi Hung} and Etienne Formstecher and Mekhala Maiti and Hazelett, {C. Clayton} and Wauson, {Eric M.} and Maria Balakireva and Camonis, {Jacques H.} and Charles Yeaman and Beth Levine and White, {Michael A.}",
year = "2011",
month = "1",
day = "21",
doi = "10.1016/j.cell.2010.12.018",
language = "English (US)",
volume = "144",
pages = "253--267",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly

AU - Bodemann, Brian O.

AU - Orvedahl, Anthony

AU - Cheng, Tzuling

AU - Ram, Rosalyn R.

AU - Ou, Yi Hung

AU - Formstecher, Etienne

AU - Maiti, Mekhala

AU - Hazelett, C. Clayton

AU - Wauson, Eric M.

AU - Balakireva, Maria

AU - Camonis, Jacques H.

AU - Yeaman, Charles

AU - Levine, Beth

AU - White, Michael A.

PY - 2011/1/21

Y1 - 2011/1/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78651488777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651488777&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2010.12.018

DO - 10.1016/j.cell.2010.12.018

M3 - Article

VL - 144

SP - 253

EP - 267

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -