{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:18:14Z","timestamp":1783055894818,"version":"3.54.6"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS-103845"],"award-info":[{"award-number":["NS-103845"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS-047332"],"award-info":[{"award-number":["NS-047332"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b1-syntrophin (\u03b1-syn) and \u03b1-dystrobrevin (\u03b1-dbn), two components of the dystrophin\u2013glycoprotein complex, are essential for the maturation and maintenance of the neuromuscular junction (NMJ) and mice deficient in either \u03b1-syn or \u03b1-dbn exhibit similar synaptic defects. However, the functional link between these two proteins and whether they exert distinct or redundant functions in the postsynaptic organization of the NMJ remain largely unknown. We generated and analyzed the synaptic phenotype of double heterozygote (\u03b1-dbn+\/\u2212, \u03b1-syn+\/\u2212), and double homozygote knockout (\u03b1-dbn\u2212\/\u2212; \u03b1-syn\u2212\/\u2212) mice and examined the ability of individual molecules to restore their defects in the synaptic phenotype. We showed that in double heterozygote mice, NMJs have normal synaptic phenotypes and no signs of muscular dystrophy. However, in double knockout mice (\u03b1-dbn\u2212\/\u2212; \u03b1-syn\u2212\/\u2212), the synaptic phenotype (the density, the turnover and the distribution of AChRs within synaptic branches) is more severely impaired than in single \u03b1-dbn\u2212\/\u2212 or \u03b1-syn\u2212\/\u2212 mutants. Furthermore, double mutant and single \u03b1-dbn\u2212\/\u2212 mutant mice showed more severe exercise-induced fatigue and more significant reductions in grip strength than single \u03b1-syn\u2212\/\u2212 mutant and wild-type. Finally, we showed that the overexpression of the transgene \u03b1-syn-GFP in muscles of double mutant restores primarily the abnormal extensions of membrane containing AChRs that extend beyond synaptic gutters and lack synaptic folds, whereas the overexpression of \u03b1-dbn essentially restores the abnormal dispersion of patchy AChR aggregates in the crests of synaptic folds. Altogether, these data suggest that \u03b1-syn and \u03b1-dbn act in parallel pathways and exert distinct functions on the postsynaptic structural organization of NMJs.<\/jats:p>","DOI":"10.1093\/hmg\/ddac041","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T15:13:23Z","timestamp":1644419603000},"page":"2370-2385","source":"Crossref","is-referenced-by-count":6,"title":["Distinct roles of the dystrophin\u2013glycoprotein complex: \u03b1-dystrobrevin and \u03b1-syntrophin in the maintenance of the postsynaptic apparatus of the neuromuscular synapse"],"prefix":"10.1093","volume":"31","author":[{"given":"Isabel Martinez-Pena y","family":"Valenzuela","sequence":"first","affiliation":[{"name":"Department of Molecular , Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular , Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Barden","sequence":"additional","affiliation":[{"name":"Department of Molecular , Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Kosloski","sequence":"additional","affiliation":[{"name":"Department of Molecular , Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-0963","authenticated-orcid":false,"given":"Mohammed","family":"Akaaboune","sequence":"additional","affiliation":[{"name":"Department of Molecular , Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA"},{"name":"Program in Neuroscience , University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"2022072316292006300_ref1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbadis.2006.05.010","article-title":"Dystrophin, its interactions with other proteins, and implications for muscular dystrophy","volume":"1772","author":"Ervasti","year":"2007","journal-title":"Biochim. 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