dystrophin associated proteins


Summary: A group of proteins that associate with DYSTROPHIN at the CELL MEMBRANE to form the DYSTROPHIN-ASSOCIATED PROTEIN COMPLEX.

Top Publications

  1. Peters M, O Brien K, Sadoulet Puccio H, Kunkel L, Adams M, Froehner S. beta-dystrobrevin, a new member of the dystrophin family. Identification, cloning, and protein associations. J Biol Chem. 1997;272:31561-9 pubmed
  2. Gee S, Madhavan R, Levinson S, Caldwell J, Sealock R, Froehner S. Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci. 1998;18:128-37 pubmed
    ..Collectively, our data suggest that syntrophins link NaChs to the actin cytoskeleton and the extracellular matrix via dystrophin and the DAPC. ..
  3. Shiao T, Fond A, Deng B, Wehling Henricks M, Adams M, Froehner S, et al. Defects in neuromuscular junction structure in dystrophic muscle are corrected by expression of a NOS transgene in dystrophin-deficient muscles, but not in muscles lacking alpha- and beta1-syntrophins. Hum Mol Genet. 2004;13:1873-84 pubmed
    ..The results suggest that defects in NMJ structure that occur in some DGC mutants can result from the secondary loss of NOS from muscle. ..
  4. Piluso G, Mirabella M, Ricci E, Belsito A, Abbondanza C, Servidei S, et al. Gamma1- and gamma2-syntrophins, two novel dystrophin-binding proteins localized in neuronal cells. J Biol Chem. 2000;275:15851-60 pubmed
    ..Our present findings suggest a differentiated role of a modified dystrophin-associated complex in the central nervous system. ..
  5. Nawrotzki R, Loh N, Ruegg M, Davies K, Blake D. Characterisation of alpha-dystrobrevin in muscle. J Cell Sci. 1998;111 ( Pt 17):2595-605 pubmed
  6. Grady R, Grange R, Lau K, Maimone M, Nichol M, Stull J, et al. Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies. Nat Cell Biol. 1999;1:215-20 pubmed
    ..These results indicate that both signalling and structural functions of the DGC are required for muscle stability, and implicate alpha-dystrobrevin in the former...
  7. Adams M, Butler M, Dwyer T, Peters M, Murnane A, Froehner S. Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution. Neuron. 1993;11:531-40 pubmed
    ..Syntrophin-2 mRNAs (2.2, 5.0, and 10 kb) are expressed in all mouse tissues examined. These patterns of expression suggest that syntrophin-1 and syntrophin-2 may associate with different members of the dystrophin family. ..
  8. Akaaboune M, Grady R, Turney S, Sanes J, Lichtman J. Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands. Neuron. 2002;34:865-76 pubmed
    ..These results demonstrate remarkable molecular dynamism underlying macroscopic stability of the postsynaptic membrane, and establish alpha-dystrobrevin as a key control point for regulation of mobility and turnover. ..
  9. Peters M, Adams M, Froehner S. Differential association of syntrophin pairs with the dystrophin complex. J Cell Biol. 1997;138:81-93 pubmed
    ..Since individual syntrophins do not have intrinsic binding specificity for dystrophin, dystrobrevin, or utrophin, the observed preferential pairing of syntrophins must depend on extrinsic regulatory mechanisms. ..

More Information


  1. Roberts R. Dystrophins and dystrobrevins. Genome Biol. 2001;2:REVIEWS3006 pubmed
    ..Despite a wealth of biochemical, cell biological and genetic information, the precise role of dystrophins, dystrobrevins and their collaborators remains unclear. ..
  2. Adams M, Tesch Y, Percival J, Albrecht D, Conhaim J, Anderson K, et al. Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by membrane-directed alpha-dystrobrevin. J Cell Sci. 2008;121:48-54 pubmed
    ..Thus, although nNOS and AQP4 both require interaction with the PDZ domain of alpha-syntrophin for sarcolemmal association, their localization is regulated differentially...
  3. Rees M, Lien C, Gorecki D. Dystrobrevins in muscle and non-muscle tissues. Neuromuscul Disord. 2007;17:123-34 pubmed
    ..As dysbindin abnormality is linked to Hermansky-Pudlak syndrome, dystrobrevins and/or their binding partners may also be required for proper function of other non-muscle tissues. ..
  4. Böhm S, Jin H, Hughes S, Roberts R, Hinits Y. Dystrobrevin and dystrophin family gene expression in zebrafish. Gene Expr Patterns. 2008;8:71-8 pubmed
  5. Dalkilic I, Kunkel L. Muscular dystrophies: genes to pathogenesis. Curr Opin Genet Dev. 2003;13:231-8 pubmed
    ..The number of genes identified increases each year, adding to our understanding as well as revealing the overall complexity of the pathogenesis of these diseases. ..
  6. Sadoulet Puccio H, Khurana T, Cohen J, Kunkel L. Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane. Hum Mol Genet. 1996;5:489-96 pubmed
    ..In addition, antibodies against either the Torpedo 87 kDa protein or human dystrobrevin demonstrate that at least three of the splice forms are translated as proteins in human brain tissue extracts. ..
  7. Jin H, Tan S, Hermanowski J, B hm S, Pacheco S, McCauley J, et al. The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms. BMC Genomics. 2007;8:19 pubmed publisher
    ..Most invertebrates studied have one member from each branch. Although the basic shared function which is implied by the common architecture of these distantly related proteins remains unclear, it clearly permeates metazoan biology...
  8. Alessi A, Bragg A, Percival J, Yoo J, Albrecht D, Froehner S, et al. gamma-Syntrophin scaffolding is spatially and functionally distinct from that of the alpha/beta syntrophins. Exp Cell Res. 2006;312:3084-95 pubmed
    ..In both neurons and muscle, gamma-syntrophin isoforms localize to the endoplasmic reticulum where they may form a scaffold for signaling and trafficking. ..
  9. Grady R, Wozniak D, Ohlemiller K, Sanes J. Cerebellar synaptic defects and abnormal motor behavior in mice lacking alpha- and beta-dystrobrevin. J Neurosci. 2006;26:2841-51 pubmed
    ..We suggest that motor deficits in muscular dystrophy patients, which are their cardinal symptoms, may reflect not only peripheral derangements but also CNS defects. ..
  10. Marchand S, Stetzkowski Marden F, Cartaud J. Differential targeting of components of the dystrophin complex to the postsynaptic membrane. Eur J Neurosci. 2001;13:221-9 pubmed
    ..This study provides the first evidence for a separate targeting of the various components of the dystrophin-associated protein complex and a step-by-step assembly at the postsynaptic membrane. ..
  11. Hogan A, Shepherd L, Chabot J, Quenneville S, Prescott S, Topham M, et al. Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions. J Biol Chem. 2001;276:26526-33 pubmed
    ..Collectively, our results suggest that gamma 1-syntrophin participates in regulating the subcellular localization of DGK-zeta to ensure correct termination of diacylglycerol signaling. ..
  12. Hoshino S, Ohkoshi N, Ishii A, Shoji S. The expression of alpha-dystrobrevin and dystrophin during skeletal muscle regeneration. J Muscle Res Cell Motil. 2002;23:131-8 pubmed
    ..6 and 5.3 days, respectively. These data provide evidence that alpha-dystrobrevin regenerates more slowly than dystrophin in skeletal muscle. ..
  13. Blake D, Hawkes R, Benson M, Beesley P. Different dystrophin-like complexes are expressed in neurons and glia. J Cell Biol. 1999;147:645-58 pubmed
    ..Thus, despite the similarity in primary sequence, alpha- and beta-dystrobrevin are differentially distributed in the brain where they form separate DPC-like complexes. ..
  14. Lien C, Vlachouli C, Blake D, Simons J, Gorecki D. Differential spatio-temporal expression of alpha-dystrobrevin-1 during mouse development. Gene Expr Patterns. 2004;4:583-93 pubmed
    ..In contrast, this specific expression at the induction phase decreased/disappeared at later stages of development. ..
  15. Allikian M, McNally E. Processing and assembly of the dystrophin glycoprotein complex. Traffic. 2007;8:177-83 pubmed
    ..Normal sarcolemmal function requires proper DGC synthesis and positioning, and perturbation of the DGC leads to muscle membrane instability and disease. ..
  16. Grady R, Akaaboune M, Cohen A, Maimone M, Lichtman J, Sanes J. Tyrosine-phosphorylated and nonphosphorylated isoforms of alpha-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctions. J Cell Biol. 2003;160:741-52 pubmed
    ..More generally, alphaDB may play multiple roles in muscle by means of differential distribution of isoforms with distinct signaling or structural properties...
  17. Gieseler K, Abdel Dayem M, Segalat L. In vitro interactions of Caenorhabditis elegans dystrophin with dystrobrevin and syntrophin. FEBS Lett. 1999;461:59-62 pubmed
    ..In vitro interaction occurs through the more conserved second helix. We propose a new model of dystrophin interactions with associated proteins. ..
  18. Sadoulet Puccio H, Feener C, Schaid D, Thibodeau S, Michels V, Kunkel L. The genomic organization of human dystrobrevin. Neurogenetics. 1997;1:37-42 pubmed
    ..Based on intronic sequence, a primer set was designed to specifically amplify each exon of dystrobrevin to screen for mutations by SSCP in patients with neuromuscular diseases for which dystrobrevin could be a candidate. ..
  19. Loh N, Newey S, Davies K, Blake D. Assembly of multiple dystrobrevin-containing complexes in the kidney. J Cell Sci. 2000;113 ( Pt 15):2715-24 pubmed
    ..Our findings also provide a possible explanation for the lack of kidney pathology in Duchenne muscular dystrophy patients and mice lacking all dystrophin isoforms. ..
  20. Rurak J, Noel G, Lui L, Joshi B, Moukhles H. Distribution of potassium ion and water permeable channels at perivascular glia in brain and retina of the Large(myd) mouse. J Neurochem. 2007;103:1940-53 pubmed
    ..1 and AQP4 to functional domains in brain, distinct mechanisms may contribute to their localization in retina. ..
  21. Adams M, Dwyer T, Dowler L, White R, Froehner S. Mouse alpha 1- and beta 2-syntrophin gene structure, chromosome localization, and homology with a discs large domain. J Biol Chem. 1995;270:25859-65 pubmed
    ..The first pleckstrin homology domain is interrupted by a domain homologous to repeated sequences originally found in the Drosophila discs-large protein. ..
  22. Ichida F, Tsubata S, Bowles K, Haneda N, Uese K, Miyawaki T, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001;103:1256-63 pubmed
    ..In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies. ..
  23. Ceccarini M, Grasso M, Veroni C, Gambara G, Artegiani B, Macchia G, et al. Association of dystrobrevin and regulatory subunit of protein kinase A: a new role for dystrobrevin as a scaffold for signaling proteins. J Mol Biol. 2007;371:1174-87 pubmed
    ..Our results suggest a new role for dystrobrevin as a scaffold protein that may play a role in different cellular processes involving PKA signaling. ..
  24. Yue Y, Liu M, Duan D. C-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice. Mol Ther. 2006;14:79-87 pubmed
    ..It also brought the response to eccentric contraction-induced injury to the normal range. In summary, our results suggest that the DeltaR4/DeltaC microgene holds great promise in preventing muscular dystrophy...
  25. Grisoni K, Martin E, Gieseler K, Mariol M, Segalat L. Genetic evidence for a dystrophin-glycoprotein complex (DGC) in Caenorhabditis elegans. Gene. 2002;294:77-86 pubmed
    ..These results strongly suggest that a protein complex comprising functional analogies with the DGC exists in C. elegans. ..
  26. Hazai D, Lien C, Hajos F, Halasy K, Gorecki D, Jancsik V. Synaptic alpha-dystrobrevin: localization of a short alpha-dystrobrevin isoform in melanin-concentrating hormone neurons of the hypothalamus. Brain Res. 2008;1201:52-9 pubmed publisher
    ..We propose that alpha-DB plays a role in a structure or regulation mechanism unique to MCH-expressing neurons. ..
  27. Newey S, Benson M, Ponting C, Davies K, Blake D. Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex. Curr Biol. 2000;10:1295-8 pubmed
    ..This is likely to have important consequences for the recruitment of specific signalling molecules to the DPC and ultimately for its function. ..
  28. Durbeej M, Campbell K. Muscular dystrophies involving the dystrophin-glycoprotein complex: an overview of current mouse models. Curr Opin Genet Dev. 2002;12:349-61 pubmed
  29. Martinez Pena y Valenzuela I, Akaaboune M. Acetylcholinesterase mobility and stability at the neuromuscular junction of living mice. Mol Biol Cell. 2007;18:2904-11 pubmed
    ..These results demonstrate that nonsynaptic AChEs are mobile, whereas synaptic AChEs are more stable, and that alpha-dystrobrevin is important for controlling the density and stability of AChEs at neuromuscular synapses. ..
  30. Blake D, Nawrotzki R, Loh N, Gorecki D, Davies K. beta-dystrobrevin, a member of the dystrophin-related protein family. Proc Natl Acad Sci U S A. 1998;95:241-6 pubmed
    ..This finding may be relevant to the cognitive dysfunction affecting many patients with Duchenne muscular dystrophy. ..
  31. Enigk R, Maimone M. Cellular and molecular properties of alpha-dystrobrevin in skeletal muscle. Front Biosci. 2001;6:D53-64 pubmed
    ..In this review, we summarize the currently known cellular and molecular properties of alpha-dystrobrevin in skeletal muscle and discuss its potential functions at both the sarcolemma and neuromuscular junction. ..
  32. Bohm S, Roberts R. Expression of members of the dystrophin, dystrobrevin, and dystrotelin superfamily. Crit Rev Eukaryot Gene Expr. 2009;19:89-108 pubmed
    ..The widespread expression in adult vertebrates, together with elaborate and dynamic patterns during development, paints a picture of a superfamily whose fundamental biological function is still poorly understood. ..
  33. Ahn A, Freener C, Gussoni E, Yoshida M, Ozawa E, Kunkel L. The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. J Biol Chem. 1996;271:2724-30 pubmed
  34. Blake D, Nawrotzki R, Peters M, Froehner S, Davies K. Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein. J Biol Chem. 1996;271:7802-10 pubmed
    ..The occurrence of many dystrobrevin isoforms is significant because alternative splicing and phosphorylation often have profound effects upon the biological activity of synaptic proteins. ..
  35. Sadoulet Puccio H, Rajala M, Kunkel L. Dystrobrevin and dystrophin: an interaction through coiled-coil motifs. Proc Natl Acad Sci U S A. 1997;94:12413-8 pubmed
    ..From the accumulated evidence of protein-protein interactions presented here and elsewhere, we propose a partially revised model of the organization of the dystrophin-associated glycoprotein complex. ..
  36. Newey S, Gramolini A, Wu J, Holzfeind P, Jasmin B, Davies K, et al. A novel mechanism for modulating synaptic gene expression: differential localization of alpha-dystrobrevin transcripts in skeletal muscle. Mol Cell Neurosci. 2001;17:127-40 pubmed
    ..Taken together, these results indicate that different isoforms possess distinct roles in synapse formation and possibly in the pathogenesis of muscular dystrophy. ..
  37. Newey S, Howman E, Ponting C, Benson M, Nawrotzki R, Loh N, et al. Syncoilin, a novel member of the intermediate filament superfamily that interacts with alpha-dystrobrevin in skeletal muscle. J Biol Chem. 2001;276:6645-55 pubmed
  38. Enigk R, Maimone M. Differential expression and developmental regulation of a novel alpha-dystrobrevin isoform in muscle. Gene. 1999;238:479-88 pubmed
  39. Hillier B, Christopherson K, Prehoda K, Bredt D, Lim W. Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science. 1999;284:812-5 pubmed
    ..This structure explains how PDZ domains can participate in diverse interaction modes to assemble protein networks. ..
  40. Roberts R, Bobrow M. Dystrophins in vertebrates and invertebrates. Hum Mol Genet. 1998;7:589-95 pubmed
  41. Claudepierre T, Dalloz C, Mornet D, Matsumura K, Sahel J, Rendon A. Characterization of the intermolecular associations of the dystrophin-associated glycoprotein complex in retinal Müller glial cells. J Cell Sci. 2000;113 Pt 19:3409-17 pubmed
  42. Benson M, Newey S, Martin Rendon E, Hawkes R, Blake D. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. J Biol Chem. 2001;276:24232-41 pubmed
    ..These findings have implications for the molecular pathology of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane. ..
  43. Ambrose H, Blake D, Nawrotzki R, Davies K. Genomic organization of the mouse dystrobrevin gene: comparative analysis with the dystrophin gene. Genomics. 1997;39:359-69 pubmed
    ..Interestingly, although there is only 27% amino acid identity between the homologous regions of dystrobrevin and dystrophin, the positions of 8 of the 15 exon-intron junctions are identical. ..
  44. Metzinger L, Blake D, Squier M, Anderson L, Deconinck A, Nawrotzki R, et al. Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy. Hum Mol Genet. 1997;6:1185-91 pubmed
    ..This is the first indication that a cytoplasmic component of the dystrophin-associated protein complex may be involved in the pathogenesis of limb-girdle muscular dystrophy. ..
  45. Mizuno Y, Thompson T, Guyon J, Lidov H, Brosius M, Imamura M, et al. Desmuslin, an intermediate filament protein that interacts with alpha -dystrobrevin and desmin. Proc Natl Acad Sci U S A. 2001;98:6156-61 pubmed
    ..Our findings suggest that DMN may serve as a direct linkage between the extracellular matrix and the Z-discs (through plectin) and may play an important role in maintaining muscle cell integrity. ..
  46. Moukhles H, Carbonetto S. Dystroglycan contributes to the formation of multiple dystrophin-like complexes in brain. J Neurochem. 2001;78:824-34 pubmed
    ..to muscle, little is known about the localization and the molecular interactions of dystrophin and dystrophin associated proteins (DAPs) in brain...
  47. Yoshida M, Hama H, Ishikawa Sakurai M, Imamura M, Mizuno Y, Araishi K, et al. Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy. Hum Mol Genet. 2000;9:1033-40 pubmed
    ..It is thus considered that the sarcoglycan-sarcospan complex is linked to the signaling protein neuronal nitric oxide synthase via alpha-syntrophin associated with dystrobrevin. ..
  48. Haenggi T, Fritschy J. Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue. Cell Mol Life Sci. 2006;63:1614-31 pubmed
    ..Here, we focus on recent studies of the DGC in brain, blood-brain barrier and choroid plexus, retina, and kidney and discuss the role of dystrophin isoforms and utrophin for assembly of the complex in these tissues...
  49. Adams M, Kramarcy N, Krall S, Rossi S, Rotundo R, Sealock R, et al. Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin. J Cell Biol. 2000;150:1385-98 pubmed
    ..Thus, alpha-syntrophin has an important role in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. ..
  50. Puca A, Nigro V, Piluso G, Belsito A, Sampaolo S, Quaderi N, et al. Identification and characterization of a novel member of the dystrobrevin gene family. FEBS Lett. 1998;425:7-13 pubmed
    ..Immunostaining studies indicate that DTN-B and DTN expression is absent in affected muscle fibers from DMD patients and carriers. ..
  51. Lumeng C, Phelps S, Crawford G, Walden P, Barald K, Chamberlain J. Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases. Nat Neurosci. 1999;2:611-7 pubmed
    ..Our data suggest that MAST205 and SAST link the dystrophin/utrophin network with microtubule filaments via the syntrophins. ..
  52. Grady R, Zhou H, Cunningham J, Henry M, Campbell K, Sanes J. Maturation and maintenance of the neuromuscular synapse: genetic evidence for roles of the dystrophin--glycoprotein complex. Neuron. 2000;25:279-93 pubmed
    ..Together, these results demonstrate involvement of distinct protein complexes in the formation and maintenance of the synapse and implicate the DGC in the latter process. ..
  53. Ahn A, Yoshida M, Anderson M, Feener C, Selig S, Hagiwara Y, et al. Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24. Proc Natl Acad Sci U S A. 1994;91:4446-50 pubmed
    ..We have mapped the human basic component of A1 and EST25263 genes to chromosomes 8q23-24 and 16, respectively. ..
  54. Ahn A, Kunkel L. Syntrophin binds to an alternatively spliced exon of dystrophin. J Cell Biol. 1995;128:363-71 pubmed
  55. Buechler C, Boettcher A, Bared S, Probst M, Schmitz G. The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex. Biochem Biophys Res Commun. 2002;293:759-65 pubmed
  56. Yang B, Ibraghimov Beskrovnaya O, Moomaw C, Slaughter C, Campbell K. Heterogeneity of the 59-kDa dystrophin-associated protein revealed by cDNA cloning and expression. J Biol Chem. 1994;269:6040-4 pubmed
    ..Our results suggest that the 59-DAP triplet may contain different protein species and that the 59-1 DAP may associate more specifically with dystrophin than with utrophin. ..