{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:47:30Z","timestamp":1784630850331,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR074988"],"award-info":[{"award-number":["R01 AR074988"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Spectrins function together with actin as obligatory subunits of the submembranous cytoskeleton. Spectrins maintain cell shape, resist mechanical forces, and stabilize ion channel and transporter protein complexes through binding to scaffolding proteins. Recently, pathogenic variants of <jats:italic>SPTBN4<\/jats:italic> (\u03b24\u00a0spectrin) were reported to cause both neuropathy and myopathy. Although the role of \u03b24\u00a0spectrin in neurons is mostly understood, its function in skeletal muscle, another excitable tissue subject to large forces, is unknown. Here, using a muscle specific \u03b24\u00a0spectrin conditional knockout mouse, we show that \u03b24\u00a0spectrin does not contribute to muscle function. In addition, we show \u03b24\u00a0spectrin is not present in muscle, indicating the previously reported myopathy associated with pathogenic <jats:italic>SPTBN4<\/jats:italic> variants is neurogenic in origin. More broadly, we show that \u03b12, \u03b21 and \u03b22\u00a0spectrins are found in skeletal muscle, with \u03b12 and \u03b21\u00a0spectrins being enriched at the postsynaptic neuromuscular junction (NMJ). Surprisingly, using muscle specific conditional knockout mice, we show that loss of \u03b12 and \u03b22\u00a0spectrins had no effect on muscle health, function or the enrichment of \u03b21\u00a0spectrin at the NMJ. Muscle specific deletion of \u03b21\u00a0spectrin also had no effect on muscle health, but, with increasing age, resulted in the loss of clustered NMJ Na<jats:sup>+<\/jats:sup> channels. Together, our results suggest that muscle \u03b21\u00a0spectrin functions independently of an associated \u03b1 spectrin to maintain Na<jats:sup>+<\/jats:sup> channel clustering at the postsynaptic NMJ. Furthermore, despite repeated exposure to strong forces and in contrast to neurons, muscles do not require spectrin cytoskeletons to maintain cell shape or integrity.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15969-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The myopathy found in pathogenic human <jats:italic>SPTBN4<\/jats:italic> variants (where <jats:italic>SPTBN4<\/jats:italic> is the gene encoding \u03b24\u00a0spectrin) is neurogenic in origin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u03b21\u00a0spectrin plays essential roles in maintaining the density of neuromuscular junction Nav1.4 Na<jats:sup>+<\/jats:sup> channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>By contrast to the canonical view of spectrin organization and function, we show that \u03b21\u00a0spectrin can function independently of an associated \u03b1 spectrin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Despite the large mechanical forces experienced by muscle, we show that spectrins are not required for muscle cell integrity. This is in stark contrast to red blood cells and the axons of neurons.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285894","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T16:43:50Z","timestamp":1709657030000},"page":"1127-1145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Postsynaptic \u03b21\u00a0spectrin maintains Na<sup>+<\/sup> channels at the neuromuscular junction"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7513-9240","authenticated-orcid":false,"given":"Ozlem","family":"Sert","sequence":"first","affiliation":[{"name":"Department of Neuroscience Baylor College of Medicine  Houston TX 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