Résumé :
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Muscle contraction is achieved when an efficient excitation signal at the plasma membrane triggers intracellular calcium release. This process called "excitationcontraction (E-C) coupling" relies on a multimolecular protein complex, the calcium release complex. This complex, spanning the plasma membrane and the sarcoplasmic reticulum (SR), is organized around the calcium channel of the SR, the ryanodine receptor (RyR1).Mutations in RyR1 lead to a number of muscle diseases: Central core disease (CCD), Multi mini core disease (MmD), centronuclear myopathy, Malignant hyperthermia& Nevertheless, the functional consequences of each mutation are largely unknown because of the lack of information on the functional domains in RyR1. For the present study, we use the mutations identified in RyR1 to decipher functional regions in RyR1. We have identified more than 200 RyR1 mutations in the course of clinical diagnosis. We have recently shown that RyR1 interacts with caveolin-3, via the transmembrane part of the channel (Vassilopoulos et al, 2010, Biochemistry, 49, 6130). Caveolin-3, which is a structural protein involved in intracellular trafficking, could therefore regulate RyR1 targeting. We are now searching for mutations in RyR1 which could affect the RyR1/Caveolin-3 interaction, to analyze the functional consequences of the disruption of this interaction, and the possible origin of the pathology.
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