Dystroglycan is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''DAG1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Dystroglycan is one of the
dystrophin
Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costa ...
-associated
glycoproteins
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
, which is encoded by a 5.5 kb transcript in ''
Homo sapiens
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
'' on
chromosome 3.
There are two
exons that are separated by a large
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
. The spliced exons code for a protein product that is finally cleaved into two non-covalently associated subunits,
lpha(N-terminal) and
eta(C-terminal).
Function
In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton.
lphadystroglycan is extracellular and binds to merosin
lpha2 laminin in the basement membrane, while
etadystroglycan is a
transmembrane
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
protein and binds to dystrophin, which is a large rod-like
cytoskeletal
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...
protein, absent in
Duchenne muscular dystrophy patients. Dystrophin binds to intracellular
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
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
Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
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,
,
[ Src,][ NCK1,][ Grb2,][
]
See also
* Dystrophin-associated protein complex
* Actin-binding protein
* Agrin
References
Further reading
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External links
*
Overview at sdbonline.org
{{Muscle tissue
Glycoproteins
Single-pass transmembrane proteins