Dystroglycan

Function

In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton. [alpha]-dystroglycan is extracellular and binds to merosin [alpha]-2 laminin in the basement membrane, while [beta]-dystroglycan is a transmembrane protein and binds to dystrophin, which is a large rod-like cytoskeletal protein, absent in Duchenne muscular dystrophy patients. Dystrophin binds to intracellular actin cables. In this way, the dystroglycan complex, which links the extracellular matrix to the intracellular actin cables, is thought to provide structural integrity in muscle tissues. The dystroglycan complex is also known to serve as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. There is also evidence which suggests the function of dystroglycan as a part of the signal transduction pathway because it is shown that Grb2, a mediator of the Ras-related signal pathway, can interact with the cytoplasmic domain of dystroglycan.

Expression

Dystroglycan is widely distributed in non-muscle tissues as well as in muscle tissues. During epithelial morphogenesis of kidney, the dystroglycan complex is shown to act as a receptor for the basement membrane. Dystroglycan expression in Mus musculus brain and neural retina has also been reported. However, the physiological role of dystroglycan in non-muscle tissues remains unclear.

In December 2022, the implications of abnormal dystroglycan expression and/or O-mannosylation on the pathogenesis of cancer have been reviewed.

Interactions

Dystroglycan has been shown to interact with FYN, C-src tyrosine kinase, Caveolin 3 and SHC1.

References

References

1. (January 1995). "Genetic mapping of the mouse neuromuscular mutation kyphoscoliosis". Genomics.
2. (February 1992). "Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix". Nature.
3. "Entrez Gene: DAG1 dystroglycan 1 (dystrophin-associated glycoprotein 1)".
4. (May 2004). "Dystroglycan, a scaffold for the ERK-MAP kinase cascade". EMBO Reports.
5. (December 2022). "Involvement of abnormal dystroglycan expression and matriglycan levels in cancer pathogenesis". Cancer Cell International.
6. (December 2001). "Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins". Biochemistry.
7. (May 1995). "SH3 domain-mediated interaction of dystroglycan and Grb2". The Journal of Biological Chemistry.
8. (December 2000). "Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members". The Journal of Biological Chemistry.