| Title: |
Huntingtin regulates calcium fluxes in skeletal muscle |
| Authors: |
Chivet, Mathilde; Mccluskey, Maximilian; Nicot, Anne Sophie; Brocard, Julie; Beaufils, Mathilde; Giovannini, Diane; Giannesini, Benoit; Poreau, Brice; Brocard, Jacques; Humbert, Sandrine; Saudou, Frédéric; Fauré, Julien; Marty, Isabelle |
| Contributors: |
GIN Grenoble Institut des Neurosciences (GIN); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA); CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA); Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Myologie Cellulaire et Pathologies; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA); Centre de résonance magnétique biologique et médicale (CRMBM); Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 0022-1295. |
| Publisher Information: |
CCSD; Rockefeller University Press |
| Publication Year: |
2023 |
| Collection: |
Université Grenoble Alpes: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; The expression of the Huntingtin protein, well known for its involvement in the neurodegenerative Huntington’s disease, has been confirmed in skeletal muscle. The impact of HTT deficiency was studied in human skeletal muscle cell lines and in a mouse model with inducible and muscle-specific HTT deletion. Characterization of calcium fluxes in the knock-out cell lines demonstrated a reduction in excitation–contraction (EC) coupling, related to an alteration in the coupling between the dihydropyridine receptor and the ryanodine receptor, and an increase in the amount of calcium stored within the sarcoplasmic reticulum, linked to the hyperactivity of store-operated calcium entry (SOCE). Immunoprecipitation experiments demonstrated an association of HTT with junctophilin 1 (JPH1) and stromal interaction molecule 1 (STIM1), both providing clues on the functional effects of HTT deletion on calcium fluxes. Characterization of muscle strength and muscle anatomy of the muscle-specific HTT-KO mice demonstrated that HTT deletion induced moderate muscle weakness and mild muscle atrophy associated with histological abnormalities, similar to the phenotype observed in tubular aggregate myopathy. Altogether, this study points toward the hypotheses of the involvement of HTT in EC coupling via its interaction with JPH1, and on SOCE via its interaction with JPH1 and/or STIM1. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36409218; PUBMED: 36409218; PUBMEDCENTRAL: PMC9682417 |
| DOI: |
10.1085/jgp.202213103 |
| Availability: |
https://inserm.hal.science/inserm-04698782; https://inserm.hal.science/inserm-04698782v1/document; https://inserm.hal.science/inserm-04698782v1/file/Huntingtin%20regulates%20calcium%20fluxes%20in%20skeletal%20muscle.pdf; https://doi.org/10.1085/jgp.202213103 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8FA2B932 |
| Database: |
BASE |