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Publication : Thin, a Trim32 ortholog, is essential for myofibril stability and is required for the integrity of the costamere in Drosophila.

First Author  LaBeau-DiMenna Elisa M Year  2012
Journal  Proc. Natl. Acad. Sci. U.S.A. Volume  109
Pages  17983-8 PubMed ID  23071324
Abstract Text  Myofibril stability is required for normal muscle function and maintenance. Mutations that disrupt myofibril stability result in individuals who develop progressive muscle wasting, or muscular dystrophy, and premature mortality. Here we present our investigations of the Drosophila l(2)thin [l(2)tn] mutant. The "thin"phenotype exhibits features of the human muscular disease phenotype in that tn mutant larvae show progressive muscular degeneration. Loss-of-function and rescue experiments determined that l(2)tn is allelic to the tn locus [previously annotated as both CG15105 and another b-box affiliate (abba)]. tn encodes a TRIM (tripartite motif) containing protein highly expressed in skeletal muscle and is orthologous to the human limb-girdle muscular dystrophy type 2H disease gene Trim32. Thin protein is localized at the Z-disk in muscle, but l(2)tn mutants showed no genetic interaction with mutants affecting the Z-line-associated protein muscle LIM protein 84B. l(2)tn, along with loss-of-function mutants generated for tn, showed no relative mislocalization of the Z-disk proteins α-Actinin and muscle LIM protein 84B. In contrast, tn mutants had significant disorganization of the costameric orthologs β-integrin, Spectrin, Talin, and Vinculin, and we present the initial description for the costamere, a key muscle stability complex, in Drosophila. Our studies demonstrate that myofibrils progressively unbundle in flies that lack Thin function through progressive costamere breakdown. Due to the high conservation of these structures in animals, we demonstrate a previously unknown role for TRIM32 proteins in myofibril stability. Doi  10.1073/pnas.1208408109
Issue  44 Month  Oct

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