title: A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy.
abstract: Autophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of the cytoplasm for delivery to the lysosome. Phosphatidylinositol 3-phosphate (PtdIns3P) produced by the class III phosphatidylinositol 3-kinase (PtdIns3K) complex is essential for canonical autophagosome formation. RAB5A, a small GTPase localized to early endosomes, has been shown to associate with the class III PtdIns3K complex, regulate its activity and promote autophagosome formation. However, little is known about how endosome-localized RAB5A functions with the class III PtdIns3K complex. Here we identified a novel endoplasmic reticulum (ER)-localized transmembrane protein, ER membrane protein complex subunit 6 (EMC6), which interacted with both RAB5A and BECN1/Beclin 1 and colocalized with the omegasome marker ZFYVE1/DFCP1. It was shown to regulate autophagosome formation, and its deficiency caused the accumulation of autophagosomal precursor structures and impaired autophagy. Our study showed for the first time that EMC6 is a novel regulator involved in autophagy.
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.forename: Liujing
authors.initials: L
authors.lastname: Qu
authors.forename: Zhenda
authors.initials: Z
authors.lastname: Wang
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D001483:Base Sequence; D000071186:Beclin-1; D002460:Cell Line; D019295:Computational Biology; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C582104:EMC6 protein, human; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D020696:rab5 GTP-Binding Proteins