{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:56:35Z","timestamp":1790834195137,"version":"4.1.0"},"reference-count":45,"publisher":"The Company of Biologists","issue":"17","license":[{"start":{"date-parts":[[1998,9,1]],"date-time":"1998-09-01T00:00:00Z","timestamp":904608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Dystrophin-related and associated proteins are important for the formation and maintenance of the mammalian neuromuscular junction. Initial studies in the electric organ of Torpedo californica showed that the dystrophin-related protein dystrobrevin (87K) co-purifies with the acetylcholine receptors and other postsynaptic proteins. Dystrobrevin is also a major phosphotyrosine-containing protein in the postsynaptic membrane. Since inhibitors of tyrosine protein phosphorylation block acetylcholine receptor clustering in cultured muscle cells, we examined the role of \u03b1-dystrobrevin during synapse formation and in response to agrin. Using specific antibodies, we show that C2 myoblasts and early myotubes only produce \u03b1-dystrobrevin-1, the mammalian orthologue of Torpedo dystrobrevin, whereas mature skeletal muscle expresses three distinct \u03b1-dystrobrevin isoforms. In myotubes, \u03b1-dystrobrevin-1 is found on the cell surface and also in acetylcholine receptor-rich domains. Following agrin stimulation, \u03b1-dystrobrevin-1 becomes re-localised beneath the cell surface into macroclusters that contain acetylcholine receptors and another dystrophin-related protein, utrophin. This redistribution is not associated with tyrosine phosphorylation of \u03b1-dystrobrevin-1 by agrin. Furthermore, we show that \u03b1-dystrobrevin-1 is associated with both utrophin in C2 cells and dystrophin in mature skeletal muscle. Thus \u03b1-dystrobrevin-1 is a component of two protein complexes in muscle, one with utrophin at the neuromuscular junction and the other with dystrophin at the sarcolemma. These results indicate that \u03b1-dystrobrevin-1 is not involved in the phosphorylation-dependent, early stages of receptor clustering, but rather in the stabilisation and maturation of clusters, possibly via an interaction with utrophin.<\/jats:p>","DOI":"10.1242\/jcs.111.17.2595","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:04:37Z","timestamp":1619370277000},"page":"2595-2605","source":"Crossref","is-referenced-by-count":75,"title":["Characterisation of \u03b1-dystrobrevin in muscle"],"prefix":"10.1242","volume":"111","author":[{"given":"Ralph","family":"Nawrotzki","sequence":"first","affiliation":[{"name":"University of Oxford 1 Genetics Unit, Department of Biochemistry , , South Parks Road, Oxford, OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nellie Y.","family":"Loh","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Genetics Unit, Department of Biochemistry , , South Parks Road, Oxford, OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Ruegg","sequence":"additional","affiliation":[{"name":"University of Basle 2 Department of Pharmacology, Biozentrum , , CH-4056 Basle, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay E.","family":"Davies","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Genetics Unit, Department of Biochemistry , , South Parks Road, Oxford, OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Blake","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Genetics Unit, Department of Biochemistry , , South Parks Road, Oxford, OX1 3QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1998,9,1]]},"reference":[{"key":"2024010700145039700_JOCES_111_17_2595C1","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1093\/emboj\/16.4.717","article-title":"Heregulin-stimulated acetylcholine receptor gene expression in muscle: Requirement for MAP kinase and evidence for a parallel inhibitory pathway independent of electrical activity","volume":"14","author":"Altiok","year":"1997","journal-title":"EMBO J"},{"key":"2024010700145039700_JOCES_111_17_2595C2","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1006\/geno.1996.4515","article-title":"Genomic organization of the mouse dystrobrevin gene: comparative analysis with the dystrophin gene","volume":"39","author":"Ambrose","year":"1997","journal-title":"Genomics"},{"key":"2024010700145039700_JOCES_111_17_2595C3","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/S0968-0004(00)88986-0","article-title":"Coiled-coil regions in the carboxy-terminal domains of dystrophin and related proteins: potentials for protein-protein interactions","volume":"20","author":"Blake","year":"1995","journal-title":"Trends Biochem. Sci"},{"key":"2024010700145039700_JOCES_111_17_2595C4","doi-asserted-by":"publisher","first-page":"7802","DOI":"10.1074\/jbc.271.13.7802","article-title":"Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein","volume":"271","author":"Blake","year":"1996","journal-title":"J. Biol. Chem"},{"key":"2024010700145039700_JOCES_111_17_2595C5","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1073\/pnas.95.1.241","article-title":"\u03b2-dystrobrevin, a member of the dystrophin-related protein family","volume":"95","author":"Blake","year":"1998","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"2024010700145039700_JOCES_111_17_2595C6","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1146\/annurev.ne.18.030195.002303","article-title":"The role of agrin in synapse formation","volume":"18","author":"Bowe","year":"1995","journal-title":"Annu. Rev. Neurosci"},{"key":"2024010700145039700_JOCES_111_17_2595C7","doi-asserted-by":"publisher","first-page":"6213","DOI":"10.1016\/S0021-9258(18)42683-X","article-title":"Association of the Mr 58,000 postsynaptic protein of electric tissue with Torpedo dystrophin and the Mr 87,000 postsynaptic protein","volume":"267","author":"Butler","year":"1992","journal-title":"J. Biol. Chem"},{"key":"2024010700145039700_JOCES_111_17_2595C8","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1083\/jcb.109.4.1753","article-title":"A novel 87,000-Mr protein associated with acetylcholine receptors in Torpedo electric organ and vertebrate skeletal muscle","volume":"109","author":"Carr","year":"1989","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C9","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1083\/jcb.136.4.883","article-title":"Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice","volume":"136","author":"Deconinck","year":"1997","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C10","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1152\/physrev.1995.75.2.339","article-title":"Acetylcholine receptor gene expression at the developing neuromuscular junction","volume":"75","author":"Duclert","year":"1995","journal-title":"Physiol. Rev"},{"key":"2024010700145039700_JOCES_111_17_2595C11","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0014-5793(95)01176-F","article-title":"Direct binding of Torpedo syntrophin to dystrophin and the 87 kDa dystrophin homologue","volume":"375","author":"Dwyer","year":"1995","journal-title":"FEBS Lett"},{"key":"2024010700145039700_JOCES_111_17_2595C12","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1083\/jcb.132.5.937","article-title":"Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation","volume":"132","author":"Ferns","year":"1996","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C13","doi-asserted-by":"publisher","first-page":"32474","DOI":"10.1074\/jbc.271.50.32474","article-title":"Functional interactions of Src family kinases with the acetylcholine receptor in C2 myotubes","volume":"271","author":"Fuhrer","year":"1996","journal-title":"J. Biol. Chem"},{"key":"2024010700145039700_JOCES_111_17_2595C14","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1083\/jcb.128.4.625","article-title":"Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site","volume":"128","author":"Gesemann","year":"1995","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C15","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1074\/jbc.273.1.600","article-title":"Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue","volume":"273","author":"Gesemann","year":"1998","journal-title":"J. Biol. Chem"},{"key":"2024010700145039700_JOCES_111_17_2595C16","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/S0092-8674(00)81252-0","article-title":"Agrin acts via a MuSK receptor complex","volume":"85","author":"Glass","year":"1996","journal-title":"Cell"},{"key":"2024010700145039700_JOCES_111_17_2595C17","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1083\/jcb.136.4.871","article-title":"Subtle neuromuscular defects in utrophin-deficient mice","volume":"136","author":"Grady","year":"1997","journal-title":"J. Cell Biol"},{"issue":"Supplement","key":"2024010700145039700_JOCES_111_17_2595C18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0092-8674(05)80031-5","article-title":"Synaptic structure and development: the neuromuscular junction","volume":"72","author":"Hall","year":"1993","journal-title":"Cell"},{"key":"2024010700145039700_JOCES_111_17_2595C19","doi-asserted-by":"publisher","first-page":"2870","DOI":"10.1016\/S0021-9258(17)42023-0","article-title":"Association of utrophin and multiple dystrophin short forms with the mammalian Mr. 58,000 dystrophin-associated protein (syntrophin)","volume":"269","author":"Kramarcy","year":"1994","journal-title":"J. Biol. Chem"},{"key":"2024010700145039700_JOCES_111_17_2595C20","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1007\/BF01187915","article-title":"Structure and function of the neuromuscular junction in young adult mdx mice","volume":"20","author":"Lyons","year":"1991","journal-title":"J. Neurocytol"},{"key":"2024010700145039700_JOCES_111_17_2595C21","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/360588a0","article-title":"Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle","volume":"360","author":"Matsumura","year":"1992","journal-title":"Nature"},{"key":"2024010700145039700_JOCES_111_17_2595C22","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1083\/jcb.131.2.441","article-title":"Immobilization of nicotinic acetylcholine receptors in mouse C2 myotubes by agrin-induced protein tyrosine phosphorylation","volume":"131","author":"Meier","year":"1995","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C23","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1002\/j.1460-2075.1996.tb00622.x","article-title":"AChR phosphorylation and aggregation induced by an agrin fragment that lacks the binding site for \u03b1-dystroglycan","volume":"15","author":"Meier","year":"1996","journal-title":"EMBO J"},{"key":"2024010700145039700_JOCES_111_17_2595C24","doi-asserted-by":"publisher","first-page":"6534","DOI":"10.1523\/JNEUROSCI.17-17-06534.1997","article-title":"Neural agrin induces ectopic postsynaptic specializations in innervated muscle fibers","volume":"17","author":"Meier","year":"1997","journal-title":"J. Neurosci"},{"key":"2024010700145039700_JOCES_111_17_2595C25","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1093\/hmg\/6.7.1185","article-title":"Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy","volume":"6","author":"Metzinger","year":"1997","journal-title":"Hum. Mol. Genet"},{"key":"2024010700145039700_JOCES_111_17_2595C26","article-title":"Molecular analysis of dystrobrevin","volume-title":"D. Phil thesis, University of Oxford","author":"Nawrotzki","year":"1997"},{"key":"2024010700145039700_JOCES_111_17_2595C27","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1083\/jcb.115.6.1695","article-title":"Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines","volume":"115","author":"Nguyen","year":"1991","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C28","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/0896-6273(91)90301-F","article-title":"Dystrophin-related protein is localized to neuromuscular junctions of adult skeletal muscle","volume":"7","author":"Ohlendieck","year":"1991","journal-title":"Neuron"},{"key":"2024010700145039700_JOCES_111_17_2595C29","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1083\/jcb.138.1.81","article-title":"Differential association of syntrophin pairs with the dystrophin complex","volume":"138","author":"Peters","year":"1997","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C30","doi-asserted-by":"publisher","first-page":"31561","DOI":"10.1074\/jbc.272.50.31561","article-title":"\u03b2-dystrobrevin, a new member of the dystrophin family","volume":"272","author":"Peters","year":"1997","journal-title":"J. Biol. Chem"},{"key":"2024010700145039700_JOCES_111_17_2595C31","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1083\/jcb.123.3.729","article-title":"Clustering and immobilization of acetylcholine receptors by the 43-kD protein: a possible role for dystrophin-related protein","volume":"123","author":"Phillips","year":"1993","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C32","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0968-0004(06)80020-4","article-title":"ZZ and TAZ: New putative zinc fingers in dystrophin and other proteins","volume":"21","author":"Ponting","year":"1996","journal-title":"Trends Biochem. Sci"},{"key":"2024010700145039700_JOCES_111_17_2595C33","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/0092-8674(81)90383-4","article-title":"All classes of intermediate filaments share a common antigenic determinant defined by a monoclonal antibody","volume":"27","author":"Pruss","year":"1981","journal-title":"Cell"},{"key":"2024010700145039700_JOCES_111_17_2595C34","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/hmg\/7.4.589","article-title":"Dystrophin in vertebrates and invertebrates","volume":"7","author":"Roberts","year":"1998","journal-title":"Hum. Mol. Genet"},{"key":"2024010700145039700_JOCES_111_17_2595C35","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/S0166-2236(97)01154-5","article-title":"Agrin orchestrates synaptic differentiation at the vertebrate neuromuscular junction","volume":"21","author":"Ruegg","year":"1998","journal-title":"Trends Neurosci"},{"key":"2024010700145039700_JOCES_111_17_2595C36","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/hmg\/5.4.489","article-title":"Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane","volume":"5","author":"Sadoulet-Puccio","year":"1996","journal-title":"Hum. Mol. Genet"},{"key":"2024010700145039700_JOCES_111_17_2595C37","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0959-4388(97)80126-2","article-title":"Genetic analysis of postsynaptic differentiation at the vertebrate neuromuscular junction","volume":"7","author":"Sanes","year":"1997","journal-title":"Curr. Opin. Neurobiol"},{"key":"2024010700145039700_JOCES_111_17_2595C38","doi-asserted-by":"publisher","first-page":"6775","DOI":"10.1523\/JNEUROSCI.16-21-06775.1996","article-title":"Aggregation of sodium channels induced by a postnatally upregulated isoform of agrin","volume":"16","author":"Sharp","year":"1996","journal-title":"J. Neurosci"},{"key":"2024010700145039700_JOCES_111_17_2595C39","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1042\/bj2870755","article-title":"Evolutionary conservation of the dystrophin central rod domain","volume":"287","author":"Sherratt","year":"1992","journal-title":"Biochem. J"},{"key":"2024010700145039700_JOCES_111_17_2595C40","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/0896-6273(93)90338-R","article-title":"The 87K postsynaptic membrane protein from Torpedo is a protein-tyrosine kinase substrate homologous to dystrophin","volume":"10","author":"Wagner","year":"1993","journal-title":"Neuron"},{"key":"2024010700145039700_JOCES_111_17_2595C41","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1046\/j.1471-4159.1994.62051947.x","article-title":"Tyrosine and serine phosphorylation of dystrophin and the 58-kDa protein in the postsynaptic membrane of Torpedo electric organ","volume":"62","author":"Wagner","year":"1994","journal-title":"J. Neurochem"},{"key":"2024010700145039700_JOCES_111_17_2595C42","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/0896-6273(91)90227-Q","article-title":"Agrin induces phosphorylation of the nicotinic acetylcholine receptor","volume":"6","author":"Wallace","year":"1991","journal-title":"Neuron"},{"key":"2024010700145039700_JOCES_111_17_2595C43","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1083\/jcb.128.6.1121","article-title":"Regulation of the interaction of nicotinic acetylcholine receptors with the cytoskeleton by agrin-activated protein tyrosine kinase","volume":"128","author":"Wallace","year":"1995","journal-title":"J. Cell Biol"},{"key":"2024010700145039700_JOCES_111_17_2595C44","doi-asserted-by":"publisher","first-page":"8194","DOI":"10.1523\/JNEUROSCI.17-21-08194.1997","article-title":"Acetylcholine receptors in innervated muscle of dystrophin mdx mice degrade as after denervation","volume":"17","author":"Xu","year":"1997","journal-title":"J. Neurosci"},{"key":"2024010700145039700_JOCES_111_17_2595C45","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/270725a0","article-title":"Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle","volume":"270","author":"Yaffe","year":"1977","journal-title":"Nature"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/111\/17\/2595\/3340286\/joces_111_17_2595.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/111\/17\/2595\/3340286\/joces_111_17_2595.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,7]],"date-time":"2024-01-07T00:15:04Z","timestamp":1704586504000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/111\/17\/2595\/25510\/Characterisation-of-dystrobrevin-in-muscle"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9,1]]},"references-count":45,"journal-issue":{"issue":"17","published-print":{"date-parts":[[1998,9,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.111.17.2595","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,9,1]]}}}