title: VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation.
abstract: We have elucidated a novel mechanism through which the autophagy-specific class III phosphatidylinositol 3-kinase (PtdIns3K) complex can be recruited to the PAS in mammalian cells, through the interaction between BECN1 and the vacuole membrane protein 1 (VMP1), an integral autophagosomal membrane protein. This interaction involves the binding between the C-terminal 20 amino acids of the VMP1 hydrophilic domain, which we have named the VMP1 autophagy-related domain (VMP1-AtgD), and the BH3 domain of BECN1. The association between these two proteins allows the formation of the autophagy-specific PtdIns3K complex, which activity favors the generation of phosphatidylinositol-3-phosphate (PtdIns3P) and the subsequent association of the autophagy-related (ATG) proteins, including ATG16L1, with the phagophore membranes. Therefore, VMP1 regulates the PtdIns3K activity on the phagophore membrane through its interaction with BECN1. Our data provide a novel model describing one of the key steps in phagophore assembly site (PAS) formation and autophagy regulation, and positions VMP1 as a new interactor of the autophagy-specific PtdIns3K complex in mammalian cells.
authors.affiliation: Institute for Biochemistry and Molecular Medicine, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Molejon
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ropolo
authors.forename: Maria I
authors.initials: MI
authors.lastname: Vaccaro
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D058546:Class III Phosphatidylinositol 3-Kinases
keywords: BECN1; VMP1; autophagy; pancreatitis; phosphatidylinositol 3-kinase