Syd/JIP3 and JNK Signaling Are Required for Myonuclear Positioning and Muscle Function

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A common pathology found in numerous cases of muscle diseases, including congenital myopathies and muscular dystrophies, is aberrantly located nuclei within individual multinucleated muscle cells. However, whether or not mispositioned myonuclei are a cause or consequence of muscle disease states is currently debated. Here, we take advantage of the model organism, Drosophila melanogaster, which shares the conserved myofiber found in mammalian systems, to identify Syd as a novel regulator of myonuclear positioning. We show that Syd is responsible for mediating the activities of Kinesin and Dynein, two motor proteins that exert forces to pull myonuclei into place. Moreover, we demonstrate that Syd-dependent myonuclear positioning also requires intracellular signaling from the JNK MAPK cascade to direct when and how myonuclei are moved into proper position. This work thus identifies developmental cues that direct proper muscle morphogenesis, suggesting that cases of muscle disease may result from a failure to achieve initial spacing of myonuclei. Supporting this notion, we find that loss of Syd impairs muscle function, but resupplying Syd restores proper myonuclear spacing and muscle function. These findings are particularly important as mispositioned myonuclei gain traction as a potential contributing factor in cases of muscle disease.

Vyšlo v časopise: Syd/JIP3 and JNK Signaling Are Required for Myonuclear Positioning and Muscle Function. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004880
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004880

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