Biology:Dystroglycan

Short description: Protein

Generic protein structure example

Dystroglycan is a protein that in humans is encoded by the DAG1 gene.

Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens on chromosome 3. There are two exons that are separated by a large intron. The spliced exons code for a protein product that is finally cleaved into two non-covalently associated subunits, [alpha] (N-terminal) and [beta] (C-terminal).

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, Src, NCK1, Grb2, Caveolin 3 and SHC1.

See also

• Dystrophin-associated protein complex
• Actin-binding protein
• Agrin

Further reading

• "Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy". Nature 359 (6393): 320–322. September 1992. doi:10.1038/359320a0. PMID 1406935. Bibcode: 1992Natur.359..320M. 
• "Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex". Neuron 15 (1): 115–126. July 1995. doi:10.1016/0896-6273(95)90069-1. PMID 7619516. 
• "SH3 domain-mediated interaction of dystroglycan and Grb2". The Journal of Biological Chemistry 270 (20): 11711–11714. May 1995. doi:10.1074/jbc.270.20.11711. PMID 7744812. 
• "Dystroglycan is a binding protein of laminin and merosin in peripheral nerve". FEBS Letters 352 (1): 49–53. September 1994. doi:10.1016/0014-5793(94)00917-1. PMID 7925941. 
• "Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor". Cell 77 (5): 675–686. June 1994. doi:10.1016/0092-8674(94)90052-3. PMID 8205617. 
• "Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization". Human Molecular Genetics 2 (10): 1651–1657. October 1993. doi:10.1093/hmg/2.10.1651. PMID 8268918. 
• "Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell membrane". The Journal of Biological Chemistry 271 (38): 23418–23423. September 1996. doi:10.1074/jbc.271.38.23418. PMID 8798547. 
• "Dystroglycan in the cerebellum is a laminin alpha 2-chain binding protein at the glial-vascular interface and is expressed in Purkinje cells". The European Journal of Neuroscience 8 (12): 2739–2747. December 1996. doi:10.1111/j.1460-9568.1996.tb01568.x. PMID 8996823. https://zenodo.org/record/1230635. 
• "A role of dystroglycan in schwannoma cell adhesion to laminin". The Journal of Biological Chemistry 272 (21): 13904–13910. May 1997. doi:10.1074/jbc.272.21.13904. PMID 9153251. 
• "Identification of novel human WW domain-containing proteins by cloning of ligand targets". The Journal of Biological Chemistry 272 (23): 14611–14616. June 1997. doi:10.1074/jbc.272.23.14611. PMID 9169421. 
• "Gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of GABA(A) receptors". The Journal of Neuroscience 34 (24): 8300–8317. June 2014. doi:10.1523/JNEUROSCI.0159-14.2014. PMID 24920633. 
• "Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue". The Journal of Biological Chemistry 273 (1): 600–605. January 1998. doi:10.1074/jbc.273.1.600. PMID 9417121. 
• "Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae". Science 282 (5396): 2076–2079. December 1998. doi:10.1126/science.282.5396.2076. PMID 9851927. Bibcode: 1998Sci...282.2076R. 
• "Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus". Science 282 (5396): 2079–2081. December 1998. doi:10.1126/science.282.5396.2079. PMID 9851928. Bibcode: 1998Sci...282.2079C. 
• "Adhesion of cultured bovine aortic endothelial cells to laminin-1 mediated by dystroglycan". The Journal of Biological Chemistry 274 (17): 11995–12000. April 1999. doi:10.1074/jbc.274.17.11995. PMID 10207021. 
• "Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses". Nature Genetics 23 (3): 338–342. November 1999. doi:10.1038/15519. PMID 10610181. 
• "The WW domain of dystrophin requires EF-hands region to interact with beta-dystroglycan". Biological Chemistry 380 (4): 431–442. April 1999. doi:10.1515/BC.1999.057. PMID 10355629. 
• "Contribution of the different modules in the utrophin carboxy-terminal region to the formation and regulation of the DAP complex". FEBS Letters 471 (2–3): 229–234. April 2000. doi:10.1016/S0014-5793(00)01400-9. PMID 10767429. 
• "Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan regulates its interaction with utrophin". Journal of Cell Science 113 ( Pt 10) (10): 1717–1726. May 2000. doi:10.1242/jcs.113.10.1717. PMID 10769203. 
• "Characterization of the beta-dystroglycan-growth factor receptor 2 (Grb2) interaction". Biochemical and Biophysical Research Communications 274 (1): 93–98. July 2000. doi:10.1006/bbrc.2000.3103. PMID 10903901. 

External links

• Dystroglycans at the US National Library of Medicine Medical Subject Headings (MeSH)
• Overview at sdbonline.org