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Proc Natl Acad Sci U S A. 2012 May 1;109(18):6981-6. doi: 10.1073/pnas.1121299109. Epub 2012 Apr 16.

Regulation of selective autophagy onset by a Ypt/Rab GTPase module.

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1
Departments of Biochemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.

Abstract

The key regulators of intracellular trafficking, Ypt/Rab GTPases, are stimulated by specific upstream activators and, when activated, recruit specific downstream effectors to mediate membrane-transport events. The yeast Ypt1 and its human functional homolog hRab1 regulate both endoplasmic reticulum (ER)-to-Golgi transport and autophagy. However, it is not clear whether the mechanism by which these GTPases regulate autophagy depends on their well-documented function in ER-to-Golgi transport. Here, we identify Atg11, the preautophagosomal structure (PAS) organizer, as a downstream effector of Ypt1 and show that the Ypt1-Atg11 interaction is required for PAS assembly under normal growth conditions. Moreover, we show that Ypt1 and Atg11 colocalize with Trs85, a Ypt1 activator subunit, and together they regulate selective autophagy. Finally, we show that Ypt1 and Trs85 interact on Atg9-containing membranes, which serve as a source for the membrane component of the PAS. Together our results define a Ypt/Rab module--comprising an activator, GTPase, and effector--that orchestrates the onset of selective autophagy, a process vital for cell homeostasis. Furthermore, because Atg11 does not play a role in ER-to-Golgi transport, we demonstrate here that Ypt/Rabs can regulate two independent membrane-transport processes by recruiting process-specific effectors.

PMID:
22509044
PMCID:
PMC3344974
DOI:
10.1073/pnas.1121299109
[Indexed for MEDLINE]
Free PMC Article
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