Drosophila ryanodine receptor gene triggers functional and developmental muscle properties and could be used to assess the impact of human RYR1 mutations
Abstract
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 Drosophila RYR gene ( dRyR ) 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 dRyR knockdown adversely affects muscle contractility, suggesting its conserved role in calcium-triggered E-C coupling. After dRyR attenuation, sarcomere, and mitochondrial patterns are severely impaired, showing dRyR involvement in structural muscle properties. However, dRyR is also prominently expressed and functionally required in growing embryonic muscles. dRyR 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 dRyR , we used Drosophila to test the impact of one human RYR1 variant of unknown significance (VUS). Larvae carrying p.Met4881Ile RYR1 VUS showed impaired mobility and altered structural muscle properties reminiscent of those seen in dRyR knockdown, thus indicating it is likely pathogenic. Overall, we show that Drosophila dRyR plays a conserved role in setting muscle contractility and structural muscle features. Our findings underline the still under-investigated role of dRyR as a promyogenic factor and provide a first example of the impact assessment of a human RYR1 VUS in Drosophila .
Related
- Drosophila Heat Shock Factor (HSF) Regulates Developmental Growth by Maintaining the Basal Expression of HSP83/HSP90
- Niche cell positioning drives functional heterogeneity in the Drosophila testis stem cell niche
- Functional dissection of Drosophila Myc cis-regulatory modules (Myc-CRMs) reveals developmentally active DNA-protein interactions
- Drosophila eIF4E paralogs: a paradigm of functional divergence
- Identification of variants of the ryanodine receptor type 1 in patients with exertional heat stroke and positive response to the malignant hyperthermia in vitro contracture test
BibTeX
@article{rendu2026drosophila,
title = {{Drosophila ryanodine receptor gene triggers functional and developmental muscle properties and could be used to assess the impact of human RYR1 mutations}},
author = {John Rendu},
journal = {eLife},
year = {2026},
month = may,
doi = {10.7554/elife.111053},
url = {https://hal.science/hal-05788807v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Drosophila ryanodine receptor gene triggers functional and developmental muscle properties and could be used to assess the impact of human RYR1 mutations
AU - John Rendu
PY - 2026
DA - 2026/05/13
JO - eLife
DO - 10.7554/elife.111053
UR - https://hal.science/hal-05788807v1
AB - 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 Drosophila RYR gene ( dRyR ) 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 dRyR knockdown adversely affects muscle contractility, suggesting its conserved role in calcium-triggered E-C coupling. After dRyR attenuation, sarcomere, and mitochondrial patterns are severely impaired, showing dRyR involvement in structural muscle properties. However, dRyR is also prominently expressed and functionally required in growing embryonic muscles. dRyR 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 dRyR , we used Drosophila to test the impact of one human RYR1 variant of unknown significance (VUS). Larvae carrying p.Met4881Ile RYR1 VUS showed impaired mobility and altered structural muscle properties reminiscent of those seen in dRyR knockdown, thus indicating it is likely pathogenic. Overall, we show that Drosophila dRyR plays a conserved role in setting muscle contractility and structural muscle features. Our findings underline the still under-investigated role of dRyR as a promyogenic factor and provide a first example of the impact assessment of a human RYR1 VUS in Drosophila .
SN - 2050-084X
ER -