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| Hauptverfasser: | , , , , , , , , |
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| Format: | Artículo científico |
| Sprache: | en |
| Veröffentlicht: |
eLife
2026
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| Schlagworte: | |
| Online-Zugang: | https://pubmed.ncbi.nlm.nih.gov/42126303/ |
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Inhaltsangabe:
- ryanodine receptor gene triggers functional and developmental muscle properties and could be used to assess the impact of human mutations. Zmojdzian, Monika Jagla, Teresa Cherik, Florian Dubinska-Magiera, Magda Migocka-Patrzałek, Marta Daczewska, Malgorzata Rendu, John Jagla, Krzysztof Sarret, Catherine Animals Ryanodine Receptor Calcium Release Channel Humans Drosophila Proteins Drosophila melanogaster Mutation Larva Muscle Development The ryanodine receptor (RYR) genes encode evolutionarily conserved calcium release channels involved in a wide range of calcium-dependent biological processes. Here, we show that the sole RYR gene () functions in differentiated somatic and cardiac muscle as well as in developing embryonic myotubes. In the larval body wall muscles, dRyR protein localizes at the SR membranes, and knockdown adversely affects muscle contractility, suggesting its conserved role in calcium-triggered E-C coupling. After attenuation, sarcomere, and mitochondrial patterns are severely impaired, showing involvement in structural muscle properties. However, is also prominently expressed and functionally required in growing embryonic muscles. loss of function leads to myotube growth defects and thin myofiber phenotypes, while its overexpression induces myofiber splitting. Given the structural and functional conservation of , we used to test the impact of one human variant of unknown significance (VUS). Larvae carrying VUS showed impaired mobility and altered structural muscle properties reminiscent of those seen in knockdown, thus indicating it is likely pathogenic. Overall, we show that plays a conserved role in setting muscle contractility and structural muscle features. Our findings underline the still under-investigated role of as a promyogenic factor and provide a first example of the impact assessment of a human VUS in .