VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation.

MOLEJÓN MI; ROPOLO A; BOGGIO V; VACCARO MI

AUTOPHAGY

LANDES BIOSCIENCE

Lugar: Austin, Texas; Año: 2013 vol. 9 p. 933 - 935

1554-8627

Autophagy. 2013 Jun 1;9(6):933-5. doi: 10.4161/auto.24390. Epub 2013 Apr 4. VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation. Molejon MI, Ropolo A, Vaccaro MI. Source 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. 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.