Transmembrane protein 49 (TMEM49, theoretical molecular weight 46kDa) also known as vacuole membrane protein 1 (VMP1) is localized to the endoplasmic reticulum of ancinar rat cells where its expression is inducible by stress (1). Expression of VMP1 is upregulated in experimental models of rat pancreatitis. In the amoeba Dictyostelium discoideum, VMP1 is critical for endoplasmic reticulum integrity and also plays a role in Dictyostelium's development (2). VMP1 localizes to the plasma membrane in cells in culture (e.g., HEK293 and Caki-2 cell lines) where it functions in cell to cell contact and regulates cell adhesion (1). Overexpression of VMP1 in vitro is associated with the formation of vacuoles and cell death (2).
VMP1 was first implicated in the process of autophagy through in vitro cell culture studies (2, 3). In mammalian cells, expression of VMP1 induces autophagy and absence of VMP1 expression inhibits autophagy. VMP1 interacts with the BH3 domain of Beclin-1 and promotes the early steps of autophagosome formation (4). VMP1 expression is implicated in various pathological conditions including type I diabetes, pancreatitis, and pancreatic cancer (4).
1. Sauermann, M., Sahin, O., Sultmann, H., Hahne, F., Blaszkiewicz, S., Majety, M.,... Arlt, D. (2008). Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells. Oncogene. https://doi.org/10.1038/sj.onc.1210743
2. Calvo-Garrido, J., Carilla-Latorre, S., Lazaro-Dieguez, F., Egea, G., & Escalante, R. (2008). Vacuole membrane protein 1 is an endoplasmic reticulum protein required for organelle biogenesis, protein secretion, and development. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.E08-01-0075
3. Calvo-Garrido, J., Carilla-Latorre, S., & Escalante, R. (2008). Vacuole membrane protein 1, autophagy and much more. Autophagy. https://doi.org/10.4161/auto.6574
4. Molejon, M. I., Ropolo, A., & Vaccaro, M. I. (2013). VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation. Autophagy. https://doi.org/10.4161/auto.24390