a Department of Molecular, Cell and Cancer Biology , University of Massachusetts Medical School , Worcester , MA USA.
b National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules , Institute of Biophysics , Chinese Academy of Sciences , Beijing , China.
Autophagy. 2018;14(2):362-363. doi: 10.1080/15548627.2017.1415591. Epub 2018 Mar 1.
The ER forms contacts with other endomembrane systems to exchange materials (e.g., calcium and lipids) and also to modulate dynamic organelle processes, including fission, cargo sorting and movement. During autophagosome formation, dynamic contacts between the ER and the phagophore membrane are crucial for phagophore expansion and closure. Little is known about the mechanisms underlying the formation and disassembly of the ER contacts. We found that the ER-localized autophagy protein EPG-3/VMP1 plays an essential role in controlling ER-phagophore dissociation and also the disassembly of ER contacts with LDs, mitochondria and endolysosomes. VMP1 regulates the ER contact by activating the ER calcium channel ATP2A/SERCA (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting). CALM (calmodulin) acts as one of the downstream calcium effectors that controls the PIK3C3/VPS34 phosphatidylinositol (PtdIns) 3-kinase (PtdIns3K) activity to maintain these contacts. Our study provides insights into the molecular mechanisms which regulate ER contacts and generate autophagosomes.
内质网（ER）与其他内膜系统形成接触以交换物质（例如钙和脂质），并调节动态细胞器过程，包括分裂、货物分拣和运动。在自噬体形成过程中，内质网和吞噬泡膜之间的动态接触对于吞噬泡的扩展和闭合至关重要。然而，内质网接触的形成和拆卸的机制知之甚少。我们发现，定位于内质网的自噬蛋白 EPG-3/VMP1 在外质网-吞噬泡解离以及内质网与脂滴、线粒体和内溶酶体接触的解体中发挥着重要作用。VMP1 通过激活内质网钙通道 ATP2A/SERCA（肌浆/内质网 Ca2+ 转运的 ATP 酶）来调节 ER 接触。CALM（钙调蛋白）作为下游钙效应物之一，控制 PIK3C3/VPS34 磷脂酰肌醇（PtdIns）3-激酶（PtdIns3K）活性来维持这些接触。我们的研究为调节内质网接触和产生自噬体的分子机制提供了深入了解。
