Reactome | Formation of the dystrophin-glycoprotein complex (DGC)

Formation of the dystrophin-glycoprotein complex (DGC)

Stable Identifier

R-HSA-9913351

DOI

10.3180/R-HSA-9913351.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Formation of the dystrophin-glycoprotein complex (DGC)

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The dystrophin-glycoprotein complex (DGC, also known as DAPC, dystrophin associated protein complex) is a large, multimeric complex of proteins and glycoproteins localized near the plasma membrane that connects the intracellular cell cytoskeleton with the extracellular matrix and laminins (reviewed in Bhat et al, 2018). In muscle cells, the DGC plays roles in stabilizing the sarcolemma and transducing mechanical stimuli (reviewed in Wilson et al, 2022), but DGC complexes are found in several other cell types and tissues and play more general roles in membrane stability, signal transduction and organization of ion channels and GABA channels (reviewed in Waite et al, 2012; Gawor and Prózyński, 2018; Bhat et al, 2018). While mutations in some components of the DGC are reported to make muscle fibers more susceptible to damage and lead to various types of muscle disorder such as Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophies and cardiomyophathies (Straub and Campbell, 1997; Cohn and Campbell, 2000), DGC components have also been associated with disorders in non-muscle tissue (Gumerson and Michele, 2011).
The core of the DGC is made up of DAG1 (dystroglycan), DMD (dystrophin) and Utrophin. DAG1 is present as a non-covalently associated alpha and beta chain following cleavage at serine 654. Extracellular alpha-DAG1 (30-653) contacts the extracellular matrix by virtue of interactions between the O-linked glycosyl groups and laminins, while the transmembrane beta-DAG1(684-895) interacts with the cytosolic dystrophin protein DMD.
The DGC also consists of a transmembrane sarcoglycan complex consisting of four sarcoglycan (SGC) proteins and SSPN (sarcospan). On the intracelluar side, DMD and beta-DAG1 recruit membrane-associated cytosolic proteins including members of the dystrobrevin (DTN) and syntrophin (SNT) families (reviewed in Bhat et al, 2018).

Literature References

PubMed ID	Title	Journal	Year
9146999	Muscular dystrophies and the dystrophin-glycoprotein complex Straub, V, Campbell, KP	Curr. Opin. Neurol.	1997
11003781	Molecular basis of muscular dystrophies Cohn, RD, Campbell, KP	Muscle Nerve	2000
22007139	The dystrophin-glycoprotein complex in the prevention of muscle damage Michele, DE, Gumerson, JD	J Biomed Biotechnol	2011
22626542	The dystrophin-glycoprotein complex in brain development and disease Brown, SC, Blake, DJ, Waite, A	Trends Neurosci	2012
28464259	ABC of multifaceted dystrophin glycoprotein complex (DGC) Dar, KB, Shah, RA, Bhat, ZF, Mir, SS, Ganai, NA, Bhat, HF	J Cell Physiol	2018
29068540	The molecular cross talk of the dystrophin-glycoprotein complex Gawor, M, Prószyński, TJ	Ann N Y Acad Sci	2018
36168044	The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction Tinker, A, Wilson, DGS, Iskratsch, T	Commun Biol	2022