| Vacuole membrane protein 1 (VMP1, TMEM49) is a transmembrane protein localized to intracellular vacuoles that was originally described as a protein promoting vacuole formation in acinar cells associated with acute pancreatitis. Over-expression of VMP1 promotes vacuole formation and subsequent cell death. Additional research studies demonstrated that VMP1 expression might be induced by starvation or the mTOR inhibitor rapamycin, which triggers autophagy. VMP1 is targeted along with LC3 to autophagosome membranes. Knockdown of VMP1 can inhibit autophagosome formation. VMP1 interacts with beclin-1, a key autophagy protein that activates the class III PI3 kinase Vps34. VMP1 functions in the degradation and clearance of zymogen-containing vacuoles during experimentally induced pancreatitis. During vacuole degradation and clearance, VMP1 interacts with the ubiquitin protease USP9X, suggesting a possible functional link between the molecular machinery of autophagy and the ubiquitin pathway. Orthologs of VMP1 from C. elegans (known as EPG-3), Drosophila (known as TANGO-5), and Dictyostelium, have been shown to play a role in membrane trafficking, organelle organization, and autophagy. |
