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Background  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.    Methodology/Principal Findings  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 α-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 in GNE overexpressing 293T cells. Furthermore, immunohistochemistry on stretched mouse muscle suggest that both GNE and α-actinin 1 localize to an overlapping but not identical region of the myofibrillar apparatus centered on the Z line.    Conclusions/Significance  The interaction of GNE with α-actinin 1 might point to its involvement in α-actinin mediated processes. In addition these studies illustrate for the first time the expression of the non-muscle form of α-actinin, α-actinin 1, in mature skeletal muscle tissue, opening novel avenues for its specific function in the sarcomere. Although no significant difference could be detected in the binding kinetics of α-actinin 1 with either wild type or mutant GNE in our SPR biosensor based analysis, further investigation is needed to determine whether and how the interaction of GNE with α-actinin 1 in skeletal muscle is relevant to the putative muscle-specific function of α-actinin 1, and to the muscle-restricted pathology of HIBM.

UDP-N-Acetylglucosamine 2-Epimerase/N-Acetylmannosamine Kinase (GNE) Binds to Alpha-Actinin 1: Novel Pathways in Skeletal Muscle?