Dystroglycan 1 (DAG1) (DAG1)

Dystroglycan 1 (DAG1) is a cell surface receptor that provides a critical linkage between the extracellular matrix and the intracellular cytoskeleton, consisting of alpha and beta subunits derived from a single precursor protein (Cao et al., 1998, Science). In the context of advanced virotherapy, alpha-dystroglycan is the primary receptor engaged by the VSV-GP glycoprotein, a chimeric protein derived from the Lymphocytic Choriomeningitis Virus (LCMV) used to replace the native G protein of Vesicular Stomatitis Virus (Goetz et al., 2020, Frontiers in Oncology). This modification, known as VSV-GP, is designed to eliminate the natural neurotropism of VSV while maintaining potent oncolytic activity against various cancers, including glioblastoma and ovarian cancer, which often express dystroglycan (Muik et al., 2014, Journal of Virology). Beyond its role as a viral entry port, DAG1 is essential for maintaining the structural integrity of muscle fibers and the blood-brain barrier, and its dysregulation is linked to muscular dystrophies and tumor progression (StatPearls, 2023). Therapeutic strategies utilizing VSV-GP exploit the high-affinity binding to alpha-dystroglycan to achieve efficient infection and lysis of tumor cells. However, because dystroglycan is widely expressed in healthy tissues, the safety profile of VSV-GP depends on the virus's sensitivity to the antiviral interferon response, which is typically defective in cancer cells but robust in normal cells.

Other names

Alpha-dystroglycanBeta-dystroglycanDystrophin-associated glycoprotein 1DAG1

Acts as the primary cellular receptor for the VSV-GP chimeric virus by binding the LCMV-derived glycoprotein, facilitating viral entry through receptor-mediated endocytosis.