Résumé :
|
In skeletal muscle, release of calcium leading to contraction (a mechanism also called “excitation contraction coupling”) is performed by a macromolecular complex, composed of two calcium channels (ryanodine receptor, RyR, and dihydropyridine receptor, DHPR). A number of associated proteins (triadin, calsequestrin, …) are also part of this complex, they could regulate the calcium channels. Mutations of RYR1 and DHPR resulting in an alteration of the calcium homeostasis have been associated with various muscle diseases including malignant hyperthermia and core associated congenital myopathies such as Central Core Disease (CCD) or Multi-mini Cores Disease (MmD). However in a number of patients, no mutation has been identified in either of the calcium channels, pointing to potential involvement of other proteins in the physiopathology of these diseases. Our research project aims at understanding the function of triadin in muscle and in the calcium release complex, and its possible involvement in these myopathies. We have previously shown that overexpression of one triadin isoform, Trisk 95, abolishes excitation-contraction coupling, and therefore that the precise stoichiometry of triadin compared to RyR seems to be important for a correct function of the calcium release complex. In order to go deeper in the identification of the function of triadin, we have developed a triadin knock-out mouse, in collaboration with ICS-Strasbourg. The first characterization (Western blot analysis, immunolabelling on muscle section) of this mouse will be presented, and the possible correlation with a human pathology will be discussed.
|