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Maturation of the muscle calcium channel DHPR in health and disease


The project aims at understanding the trafficking and maturation of the ?1S subunit of dihydropyridine receptor (DHPR), a calcium channel essential for muscle contraction, and thus reveal the consequences of truncating mutations identified at proximity of a cleavage site in some myopathy patients.


Some congenital myopathies are due to mutations in the gene encoding the ?1S subunit of the voltage-gated calcium channel DHPR involved in excitation-contraction coupling. Patients suffer from neonatal hypotonia and generalized weakness and no treatment has been found. Some recessive mutations have been identified at proximity of DHPR?1S cleavage site whose function remains elusive. In order to elucidate the trafficking of DHPR?1S and the normal functions of its cleavage, DHPR?1S cleavable and uncleavable forms, as well as cleaved N-ter and C-ter fragments will be expressed in muscle cells. The localization and trafficking of the different forms will be assessed by fixed and live-imaging microscopy. The same readouts will be observed in primary muscle cells derived from patient biopsies to understand the consequences of truncating mutations.
This project will allow to better understand the trafficking and maturation of a protein essential for muscle contraction. Such understanding might reveal targeted therapeutical strategies for the patients.


Methods used will include molecular biology, biochemistry, cell culture and live-imaging microscopy in cell lines and primary cultures of mouse and human muscle cells.


  • Sébastien et al. (2020) Dynamics of triadin, a muscle-specific triad protein, within sarcoplasmic reticulum subdomains. Mol Biol Cell. 31(4):261-272.
  • Osseni et al. (2016) Triadin and CLIMP-63 form a link between triads and microtubules in muscle cells. J Cell Sci. 2016. 129(20):3744-3755.

Domaines d'expertise requis

molecular biology, biochemistry, cell biology.


A.-S. Nicot, MCU UGA
Email :
Tél: 04 56 52 05 70


Mise à jour le 26 juin 2020


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