{"doi":"10.3389/fcell.2023.1209542","title":"Detyrosinated microtubule arrays drive myofibrillar malformations in mdx muscle fibers","abstract":"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 ( mdx ), myofibrillar alterations are abundant in advanced pathology (>4 months), 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 weeks) with no evidence myofibrillar alterations. At 16 weeks, 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 mdx muscle at 4 weeks. Using the genetic increase in VASH2/SVBP expression in 4 weeks wild-type mice we find densified deTyr-enriched MT arrays that co-segregate with myofibrillar malformations similar to those in the 16 weeks mdx . 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.","journal":"Frontiers in Cell and Developmental Biology","year":2023,"id":367332,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307450,"name":"Tessa Altair Morris","orcid":"0000-0002-7649-4364","position":1,"is_corresponding":false},{"id":1124919,"name":"Camilo Vanegas","orcid":null,"position":2,"is_corresponding":false},{"id":314331,"name":"Jacob G. Kallenbach","orcid":"0000-0002-0405-1521","position":3,"is_corresponding":false},{"id":1124920,"name":"Kaylie Pinto","orcid":null,"position":4,"is_corresponding":false},{"id":291300,"name":"Humberto C. Joca","orcid":"0000-0001-7658-504X","position":5,"is_corresponding":false},{"id":814308,"name":"Marie‐Jo Moutin","orcid":"0000-0003-2681-9818","position":6,"is_corresponding":false},{"id":243709,"name":"Guoli Shi","orcid":null,"position":7,"is_corresponding":false},{"id":1124481,"name":"Jeanine A. Ursitti","orcid":"0000-0002-6842-0488","position":8,"is_corresponding":false},{"id":307455,"name":"Anna Grosberg","orcid":"0000-0002-8878-0843","position":9,"is_corresponding":false},{"id":291299,"name":"Christopher W. Ward","orcid":"0000-0001-6774-3579","position":10,"is_corresponding":false},{"id":676490,"name":"Anicca Harriot","orcid":"0000-0002-0846-3769","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:15:12.215513Z","pmid":"37691825","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}