論文 - 詳細
| RRC ID | 51492 |
|---|---|
| 著者 | Zhao YG, Chen Y, Miao G, Zhao H, Qu W, Li D, Wang Z, Liu N, Li L, Chen S, Liu P, Feng D, Zhang H. |
| タイトル | The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. |
| ジャーナル | Mol Cell |
| Abstract |
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 ER-IM 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 (sarco[endo]plasmic reticulum calcium ATPase) 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. |
| 巻・号 | 67(6) |
| ページ | 974-989.e6 |
| 公開日 | 2017-9-21 |
| DOI | 10.1016/j.molcel.2017.08.005 |
| PII | S1097-2765(17)30579-8 |
| PMID | 28890335 |
| MeSH | Animals Animals, Genetically Modified Autophagosomes / enzymology* Autophagy-Related Protein-1 Homolog / genetics Autophagy-Related Protein-1 Homolog / metabolism Autophagy-Related Proteins COS Cells CRISPR-Cas Systems Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Calcium-Binding Proteins / metabolism Chlorocebus aethiops Endoplasmic Reticulum / enzymology* Genotype HEK293 Cells HeLa Cells Humans Intracellular Membranes / enzymology* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Lipid Droplets / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism* Muscle Proteins / metabolism Phenotype Phosphatidylinositol Phosphates / metabolism Proteolipids / metabolism RNA Interference Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism* Transfection |
| IF | 15.584 |
| 引用数 | 51 |
| リソース情報 | |
| 線虫 | tm1108 |