Résumé :
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Hereditary inclusion body myopathy (HIBM) is a rare neuromuscular disorder caused by mutations in GNE, the key enzyme in the biosynthetic pathway of sialic acid. While the mechanism leading from GNE mutations to the HIBM phenotype is not yet understood, we searched for proteins potentially interacting with GNE, which could give some insights about novel putative biological functions of GNE in muscle. We used a Surface Plasmon Resonance (SPR)-Biosensor based assay to search for potential GNE interactors in anion exchanged fractions of human skeletal muscle primary culture cell lysate. Analysis of the positive fractions by in vitro binding assay revealed ? -actinin 1 as a potential interactor of GNE. The direct interaction of the two proteins was assessed in vitro by SPR-Biosensor based kinetics analysis and in a cellular environment by a co-immunoprecipitation assay and confocal co-localization in 293T cells. The interaction of GNE with ? -actinin 1 might point to its involvement in ?-actinin mediated processes, including cytoskeleton organization and signaling pathways. In addition these studies illustrate for the first time the expression of the non-muscle form of ? -actinin, ? -actinin 1, in mature skeletal muscle tissue, opening novel avenues for its specific function in the sarcomere.
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