Dystroglycan is one of the
dystrophin-associated
glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens on
chromosome 3.[8] 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.[9]
Yamada H, Shimizu T, Tanaka T, Campbell KP, Matsumura K (September 1994). "Dystroglycan is a binding protein of laminin and merosin in peripheral nerve". FEBS Letters. 352 (1): 49–53.
doi:
10.1016/0014-5793(94)00917-1.
PMID7925941.
S2CID17529055.
Gee SH, Montanaro F, Lindenbaum MH, Carbonetto S (June 1994). "Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor". Cell. 77 (5): 675–686.
doi:
10.1016/0092-8674(94)90052-3.
PMID8205617.
S2CID54232250.
Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, Yang B, Koepnick K, Francke U, Campbell KP (October 1993). "Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization". Human Molecular Genetics. 2 (10): 1651–1657.
doi:
10.1093/hmg/2.10.1651.
PMID8268918.
Rambukkana A, Yamada H, Zanazzi G, Mathus T, Salzer JL, Yurchenco PD, et al. (December 1998). "Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae". Science. 282 (5396): 2076–2079.
Bibcode:
1998Sci...282.2076R.
doi:
10.1126/science.282.5396.2076.
PMID9851927.
Cao W, Henry MD, Borrow P, Yamada H, Elder JH, Ravkov EV, et al. (December 1998). "Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus". Science. 282 (5396): 2079–2081.
Bibcode:
1998Sci...282.2079C.
doi:
10.1126/science.282.5396.2079.
PMID9851928.
Côté PD, Moukhles H, Lindenbaum M, Carbonetto S (November 1999). "Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses". Nature Genetics. 23 (3): 338–342.
doi:
10.1038/15519.
PMID10610181.
S2CID564897.
Rentschler S, Linn H, Deininger K, Bedford MT, Espanel X, Sudol M (April 1999). "The WW domain of dystrophin requires EF-hands region to interact with beta-dystroglycan". Biological Chemistry. 380 (4): 431–442.
doi:
10.1515/BC.1999.057.
PMID10355629.
S2CID24598356.
Tommasi di Vignano A, Di Zenzo G, Sudol M, Cesareni G, Dente L (April 2000). "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.
doi:
10.1016/S0014-5793(00)01400-9.
PMID10767429.
S2CID21529759.
Russo K, Di Stasio E, Macchia G, Rosa G, Brancaccio A, Petrucci TC (July 2000). "Characterization of the beta-dystroglycan-growth factor receptor 2 (Grb2) interaction". Biochemical and Biophysical Research Communications. 274 (1): 93–98.
doi:
10.1006/bbrc.2000.3103.
PMID10903901.
Dystroglycan is one of the
dystrophin-associated
glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens on
chromosome 3.[8] 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.[9]
Yamada H, Shimizu T, Tanaka T, Campbell KP, Matsumura K (September 1994). "Dystroglycan is a binding protein of laminin and merosin in peripheral nerve". FEBS Letters. 352 (1): 49–53.
doi:
10.1016/0014-5793(94)00917-1.
PMID7925941.
S2CID17529055.
Gee SH, Montanaro F, Lindenbaum MH, Carbonetto S (June 1994). "Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor". Cell. 77 (5): 675–686.
doi:
10.1016/0092-8674(94)90052-3.
PMID8205617.
S2CID54232250.
Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, Yang B, Koepnick K, Francke U, Campbell KP (October 1993). "Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization". Human Molecular Genetics. 2 (10): 1651–1657.
doi:
10.1093/hmg/2.10.1651.
PMID8268918.
Rambukkana A, Yamada H, Zanazzi G, Mathus T, Salzer JL, Yurchenco PD, et al. (December 1998). "Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae". Science. 282 (5396): 2076–2079.
Bibcode:
1998Sci...282.2076R.
doi:
10.1126/science.282.5396.2076.
PMID9851927.
Cao W, Henry MD, Borrow P, Yamada H, Elder JH, Ravkov EV, et al. (December 1998). "Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus". Science. 282 (5396): 2079–2081.
Bibcode:
1998Sci...282.2079C.
doi:
10.1126/science.282.5396.2079.
PMID9851928.
Côté PD, Moukhles H, Lindenbaum M, Carbonetto S (November 1999). "Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses". Nature Genetics. 23 (3): 338–342.
doi:
10.1038/15519.
PMID10610181.
S2CID564897.
Rentschler S, Linn H, Deininger K, Bedford MT, Espanel X, Sudol M (April 1999). "The WW domain of dystrophin requires EF-hands region to interact with beta-dystroglycan". Biological Chemistry. 380 (4): 431–442.
doi:
10.1515/BC.1999.057.
PMID10355629.
S2CID24598356.
Tommasi di Vignano A, Di Zenzo G, Sudol M, Cesareni G, Dente L (April 2000). "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.
doi:
10.1016/S0014-5793(00)01400-9.
PMID10767429.
S2CID21529759.
Russo K, Di Stasio E, Macchia G, Rosa G, Brancaccio A, Petrucci TC (July 2000). "Characterization of the beta-dystroglycan-growth factor receptor 2 (Grb2) interaction". Biochemical and Biophysical Research Communications. 274 (1): 93–98.
doi:
10.1006/bbrc.2000.3103.
PMID10903901.