Huntingtin regulates calcium fluxes in skeletal muscle - Grenoble Institut Neurociences
Article Dans Une Revue Journal of General Physiology Année : 2023

Huntingtin regulates calcium fluxes in skeletal muscle

Résumé

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.
Fichier principal
Vignette du fichier
Huntingtin regulates calcium fluxes in skeletal muscle.pdf (4.3 Mo) Télécharger le fichier
Origine Publication financée par une institution
licence

Dates et versions

inserm-04698782 , version 1 (16-09-2024)

Licence

Identifiants

Citer

Mathilde Chivet, Maximilian Mccluskey, Anne Sophie Nicot, Julie Brocard, Mathilde Beaufils, et al.. Huntingtin regulates calcium fluxes in skeletal muscle. Journal of General Physiology, 2023, 155 (1), pp.e202213103. ⟨10.1085/jgp.202213103⟩. ⟨inserm-04698782⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

More