Journal
MOLECULAR CELL
Volume 67, Issue 6, Pages 974-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2017.08.005
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Funding
- NSFC [31421002, 31561143001, 31630048, 31671430, 31401184, 31401175]
- National Basic Research Program of China [2013CB910100]
- Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) [XDB19000000]
- Key Research Program of Frontier Sciences, CAS [QYZDY-SSW-SMC006]
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q During autophagosome formation in mammalian cells, isolation membranes (IMs; autophagosome precursors) dynamically contact the ER. Here, we demonstrated that the ER-localized metazoan-specific autophagy protein EPG-3/VMP1 controls ERIM contacts. Loss of VMP1 causes stable association of IMs with the ER, thus blocking autophagosome formation. Interaction of WIPI2 with the ULK1/FIP200 complex and PI(3) P contributes to the formation of ER-IM contacts, and these interactions are enhanced by VMP1 depletion. VMP1 controls contact formation by promoting SERCA (sarcoendo] plasmic reticulum calciumATPase) activity. VMP1 interacts with SERCA and prevents formation of the SERCA/PLN/SLN inhibitory complex. VMP1 also modulates ER contacts with lipid droplets, mitochondria, and endosomes. These ER contacts are greatly elevated by the SERCA inhibitor thapsigargin. Calmodulin acts as a sensor/effector to modulate the ER contacts mediated by VMP1/SERCA. Our study provides mechanistic insights into the establishment and disassociation of ER-IM contacts and reveals that VMP1 modulates SERCA activity to control ER contacts.
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