9.B.277. The Dystroglycan (DG) Family
The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization. Alpha-dystroglycan is an extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains. It is a receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells. Beta-dystroglycan (β-dystroglycan; 895 aas, 2 TMSs) is a transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. It has the ability to target to the nuclear envelope to maintain nuclear architecture.
Vélez-Aguilera et al. 2018 showed that beta-DG has a nuclear export pathway in myoblasts that depends on the recognition of a nuclear export signal located in its C-terminal TMS. Mutations caused β-DG nuclear accumulation, resulting in mislocalization and decreased levels of emerin and lamin B1 as well as disruption of various nuclear processes in which emerin (centrosome-nucleus linkage and beta-catenin transcriptional activity) and lamin B1 (cell cycle progression and nucleoli structure) are involved.Thus, control of nuclear beta-DG content is physiologically important to preserve proper nuclear envelope structure and activity (Vélez-Aguilera et al. 2018).