Reactome | Recruitment of dystrophin, dystrobrevin and syntrophin proteins to the DGC

Recruitment of dystrophin, dystrobrevin and syntrophin proteins to the DGC

Stable Identifier

R-HSA-9913339

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Recruitment of dystrophin, dystrobrevin and syntrophin proteins to the DGC

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Once at the plasma membrane, the core cytosolic components of the assembling dystrophin-glycoprotein complex (DGC) are recruited. These include dystrophin (DMD) or related proteins utrophin (UTRN) or dystrophin-related protein 2 (DRP2), the dystrobrevin proteins (DTNA and/or DTNB) and member(s) of the syntrophin family (SNTA1, SNTB1, SNTB2, SNTG1 or SNTG2).
Dystrophin (DMD) is the largest known gene in the human genome at 2.4 million base pairs. It is widely expressed in brain, muscle, kidney lung and testis, and has multiple transcriptional isoforms (Lederfein et al, 1992; reviewed in Bhat et al, 2018). Dystrophin interacts with the cytosplasmic domain of transmembrane dystroglycan-beta (DAG1(654-895)), as well as with other components of the cytosolic DGC complex including the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2, and dystrobrevins DTNA and DTNB (Chung and Campanelli, 1999; Huang et al, 2000; Jung et al, 1995; Ilsey et al, 2001; Ahn et al, 1995; Ahn et al, 1996; Sadoulet-Puccio et al, 1996; Sadoulet-Puccio et al, 1997; Suzuki et al, 1994). Utrophin (UTRN, "ubiquitous dystrophin") is a dystrophin homologue that is widely expressed, particularly during embryogenesis and gradually replaced by dystrophin at birth. UTRN is retained in some tissues and can partially compensate for deletion of DMD (reviewed in Bhat et al, 2018). Dystrophin-related protein 2 (DRP2) is another DMD-related protein that is found in some DGC complexes, notably in Schwann cells (Yamada et al, 1994; Yamada et al, 1996; Sherman et al, 2001).
The C-terminal region of dystrophin interacts with two families of cytosolic proteins, the dystrobrevins and the syntrophins. Two genes code for dystrobrevin proteins, DTNA (dystrobrevin alpha, primarily expressed in skeletal and cardiac muscle) and DTNB (dystrobrevin beta, primarily expressed in brain, kidney and pancreas). Based on studies in mouse, DTN proteins additionally bind members of the syntrophin family in a manner that is independent of their DMD-binding (Blake et al, 1999; Peters et al, 1997; Madhavan and Jarrett, 1995; Yoshida et al, 2000).
There are five syntrophin genes in the human genome, alpha, beta 1, beta 2, gamma 1 and gamma 2, encoded by SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2 respectively. SNTA1 is highly expressed in heart and skeletal muscle, SNTB1 and SNTB2 are widely expressed in many tissues and SNTG1 and SNTG2 are predominantly expressed in brain, as well as in other tissue. The SNT proteins participate in the DGC complex as either monomers or dimers, and bind both to DTN proteins and directly to the C-terminal region of DMD (Peters et al, 1997; Madhavan and Jarrett, 1995; Loh et al, 2000). Syntrophin proteins additionally bind to numerous other proteins including kinases, sodium channels and nitric-oxide synthase, among others, and may work to help transmit mechanical stresses into signaling cascades (Gee et al, 1998; Hogan et al, 2001; Adams et al, 2001; Abdelmoity et al, 2000; Kobzik et al, 1994).

Literature References

PubMed ID	Title	Journal	Year
10932245	Structure of a WW domain containing fragment of dystrophin in complex with beta-dystroglycan Huang, X, Poy, F, Zhang, R, Joachimiak, A, Sudol, M, Eck, MJ	Nat Struct Biol	2000
8845841	Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane Sadoulet-Puccio, HM, Khurana, TS, Cohen, JB, Kunkel, LM	Hum Mol Genet	1996
11571312	In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4 Adams, ME, Mueller, HA, Froehner, SC	J Cell Biol	2001
9356463	Dystrobrevin and dystrophin: an interaction through coiled-coil motifs Sadoulet-Puccio, HM, Rajala, M, Kunkel, LM	Proc Natl Acad Sci U S A	1997
28464259	ABC of multifaceted dystrophin glycoprotein complex (DGC) Bhat, HF, Mir, SS, Dar, KB, Bhat, ZF, Shah, RA, Ganai, NA	J Cell Physiol	2018
11495720	The interaction of dystrophin with beta-dystroglycan is regulated by tyrosine phosphorylation Ilsley, JL, Sudol, M, Winder, SJ	Cell Signal	2001
1319059	A 71-kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues Lederfein, D, Levy, Z, Augier, N, Mornet, D, Morris, G, Fuchs, O, Yaffe, D, Nudel, U	Proc Natl Acad Sci U S A	1992
7844150	Syntrophin binds to an alternatively spliced exon of dystrophin Ahn, AH, Kunkel, LM	J Cell Biol	1995
11352924	Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions Hogan, A, Shepherd, L, Chabot, J, Quenneville, S, Prescott, SM, Topham, MK, Gee, SH	J Biol Chem	2001
7592992	Identification and characterization of the dystrophin anchoring site on beta-dystroglycan Jung, D, Yang, B, Meyer, J, Chamberlain, JS, Campbell, KP	J Biol Chem	1995
7925941	Dystroglycan is a binding protein of laminin and merosin in peripheral nerve Yamada, H, Shimizu, T, Tanaka, T, Campbell, KP, Matsumura, K	FEBS Lett.	1994
7527495	Nitric oxide in skeletal muscle Kobzik, L, Reid, MB, Bredt, DS, Stamler, JS	Nature	1994
8125086	Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin Suzuki, A, Yoshida, M, Hayashi, K, Mizuno, Y, Hagiwara, Y, Ozawa, E	Eur J Biochem	1994
8798547	Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell membrane Yamada, H, Denzer, AJ, Hori, H, Tanaka, T, Anderson, LV, Fujita, S, Fukuta-Ohi, H, Shimizu, T, Ruegg, MA, Matsumura, K	J. Biol. Chem.	1996
9214383	Differential association of syntrophin pairs with the dystrophin complex Peters, MF, Adams, ME, Froehner, SC	J Cell Biol	1997
10545507	Different dystrophin-like complexes are expressed in neurons and glia Blake, DJ, Hawkes, R, Benson, MA, Beesley, PW	J Cell Biol	1999
10767327	Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy Yoshida, M, Hama, H, Ishikawa-Sakurai, M, Imamura, M, Mizuno, Y, Araishi, K, Wakabayashi-Takai, E, Noguchi, S, Sasaoka, T, Ozawa, E	Hum Mol Genet	2000
8627307	Characterization of dystroglycan-laminin interaction in peripheral nerve Yamada, H, Chiba, A, Endo, T, Kobata, A, Anderson, LV, Hori, H, Fukuta-Ohi, H, Kanazawa, I, Campbell, KP, Shimizu, T, Matsumura, K	J. Neurochem.	1996
10893187	Assembly of multiple dystrobrevin-containing complexes in the kidney Loh, NY, Newey, SE, Davies, KE, Blake, DJ	J Cell Sci	2000
7547961	Interactions between dystrophin glycoprotein complex proteins Madhavan, R, Jarrett, HW	Biochemistry	1995
9412493	Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins Gee, SH, Madhavan, R, Levinson, SR, Caldwell, JH, Sealock, R, Froehner, SC	J Neurosci	1998
8576247	The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives Ahn, AH, Freener, CA, Gussoni, E, Yoshida, M, Ozawa, E, Kunkel, LM	J Biol Chem	1996
10662592	WW and EF hand domains of dystrophin-family proteins mediate dystroglycan binding Chung, W, Campanelli, JT	Mol Cell Biol Res Commun	1999
1556129	Association of the Mr 58,000 postsynaptic protein of electric tissue with Torpedo dystrophin and the Mr 87,000 postsynaptic protein Butler, MH, Douville, K, Murnane, AA, Kramarcy, NR, Cohen, JB, Sealock, R, Froehner, SC	J Biol Chem	1992
11430802	Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy Sherman, DL, Fabrizi, C, Gillespie, CS, Brophy, PJ	Neuron	2001