Detyrosinated microtubule arrays drive myofibrillar malformations in mdx muscle fibers
Author
Harriot, AniccaAltair-Morris, Tessa
Vanegas, Camilo
Kallenbach, Jacob G.
Pinto, Kaylie
Joca, Humberto C.
Moutin, Marie-Jo
Shi, Guoli
Ursitti, Jeanine Anne
Grosberg, Anna
Ward, Christopher W.
Date
2024-06-24Type
Poster/Presentation
Metadata
Show full item recordAbstract
Altered myofibrillar structure is a consequence of dystrophic pathology that impairs skeletal muscle contractile function and increases susceptibility to contraction injury1–3. In murine Duchenne muscular dystrophy (mdx), myofibrillar alterations are abundant in advanced pathology (>4 months) 1–3, an age where we formerly established densified microtubule (MT) arrays enriched in detyrosinated (deTyr) tubulin as negative disease modifiers impacting cell mechanics and mechanotransduction4,5. Given the essential role of deTyr-enriched MT’s in myofibrillar growth, maintenance, and repair, we examined the increased abundance of these arrays as a potential mechanism for these myofibrillar alterations. Here (see6 ) 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 wks. Using the genetic increase in VASH2/SVBP expression in 4 wk wild-type mice we find densified deTyrenriched MT arrays that co-segregate with myofibrillar malformations similar to those in the 16 wk mdx. Given that no changes 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.Description
New Directions in Muscle Biology. June 24, 2024.Rights/Terms
Attribution-NonCommercial-NoDerivatives 4.0 InternationalIdentifier to cite or link to this item
http://hdl.handle.net/10713/22579Collections
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