TMEM49: Lysates

Transmembrane protein 49 (TMEM49), also known as vacuole membrane protein 1 (VMP1), is an endoplasmic reticulum (ER)-localized protein that plays an important role in autophagy and, specifically, autophagosome formation (1). TMEM49/VMP1 is synthesized as 406 amino acid (aa) transmembrane protein containing a VTT (VMP1-TMEM41b-TVP38) domain and with a theoretical molecular weight of 46 kDa (1,2). TMEM49 helps regulate ER contacts with membranes such as isolation membranes, mitochondria, endosomes, and lipid droplets (1). TMEM49/VMP1 deficiency leads to tighter ER contacts and, in the context of autophagy, results in failure of the autophagosome and lysosome to fuse and eventual disruption of autophagic flux (1).

TMEM49/VMP1 was first implicated in pancreatitis and its overexpression, together with KRAS oncogene activation, leads to development of pancreatic ductal adenocarcinoma (PDAC) (3). Aside from pancreatitis, TMEM49/VMP1 is also associated with a number of other pathologies including cancer, inflammatory bowel disease, and, potentially, neurodegenerative disorders such as Parkinson's Disease (PD) and Alzheimer's Disease (AD) (1). It is suggested that TMEM49/VMP1 deficiency in neurons results in disrupted autophagy and protein aggregation, increased ER-membrane contacts, and dysfunctional mitochondrial homeostasis, all of which contribute to neurodegeneration (1).

References

1. Wang, P., Kou, D., & Le, W. (2020). Roles of VMP1 in Autophagy and ER-Membrane Contact: Potential Implications in Neurodegenerative Disorders. Frontiers in molecular neuroscience, 13, 42. https://doi.org/10.3389/fnmol.2020.00042

2. Uniprot (Q96GC9)

3. Iovanna J. L. (2016). Autophagy Induced during Pancreatitis Promotes KRAS-Dependent Transformation in the Pancreas. Frontiers in oncology, 6, 226. https://doi.org/10.3389/fonc.2016.00226