{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:08:06Z","timestamp":1785222486629,"version":"3.55.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Altered myofibrillar structure is a consequence of dystrophic pathology that impairs skeletal muscle contractile function and increases susceptibility to contraction injury. In murine Duchenne muscular dystrophy (<jats:italic>mdx<\/jats:italic>), myofibrillar alterations are abundant in advanced pathology (&amp;gt;4\u00a0months), an age where we formerly established densified microtubule (MT) arrays enriched in detyrosinated (deTyr) tubulin as negative disease modifiers impacting cell mechanics and mechanotransduction. Given the essential role of deTyr-enriched MT arrays in myofibrillar growth, maintenance, and repair, we examined the increased abundance of these arrays as a potential mechanism for these myofibrillar alterations. Here we find an increase in deTyr-tubulin as an early event in dystrophic pathology (4\u00a0weeks) with no evidence myofibrillar alterations. At 16\u00a0weeks, we show deTyr-enriched MT arrays significantly densified and co-localized to areas of myofibrillar malformation. Profiling the enzyme complexes responsible for deTyr-tubulin, we identify vasohibin 2 (VASH2) and small vasohibin binding protein (SVBP) significantly elevated in the <jats:italic>mdx<\/jats:italic> muscle at 4\u00a0weeks. Using the genetic increase in VASH2\/SVBP expression in 4\u00a0weeks wild-type mice we find densified deTyr-enriched MT arrays that co-segregate with myofibrillar malformations similar to those in the 16\u00a0weeks <jats:italic>mdx<\/jats:italic>. Given that no changes in sarcomere organization were identified in fibers expressing sfGFP as a control, we conclude that disease-dependent densification of deTyr-enriched MT arrays underscores the altered myofibrillar structure in dystrophic skeletal muscle fibers.<\/jats:p>","DOI":"10.3389\/fcell.2023.1209542","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:55:06Z","timestamp":1692982506000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Detyrosinated microtubule arrays drive myofibrillar malformations in mdx muscle fibers"],"prefix":"10.3389","volume":"11","author":[{"given":"Anicca D.","family":"Harriot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Altair Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Vanegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Kallenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylie","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto C.","family":"Joca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jo","family":"Moutin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoli","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine A.","family":"Ursitti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Grosberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1126\/science.aao4165","article-title":"Vasohibins\/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation","volume":"1453","author":"Aillaud","year":"2017","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1249\/00005768-199408000-00007","article-title":"Muscle fiber splitting in stretch-enlarged avian muscle","volume":"26","author":"Antonio","year":"1994","journal-title":"Med. 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