Abstract:
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Communication n° 61. Tropomyosins belong to a family of highly conserved proteins expressed in muscle and non muscle cells. Tropomyosin is a key contractile protein with two chains coiled that binds along the length of the actin filament and involved in the regulation of the actomyosin interaction. Tropomyosin regulates Ca2+ mediated actin-myosin crossbridging though steric hindrance, allosteric and cooperative mechanisms. Tropomyosins are encoded by a four member multigene family: alpha-TM, beta-TM, TPM3, TPM4. While alpha-TM and beta-TM are well characterized in skeletal muscle, less is known about the expression of other isoforms in skeletal muscle as well as the plasticity of TM expression during atrophy. We also analyzed the expression and post-translational modifications of Tm in rat in control conditions and in a model of functional atrophy (Hindlimb Unloading or HU) as well as in human skeletal muscle affected by infantile spinal amyotrophy (ISA), using 2D electrophoresis and MALDI TOF. Three isoforms of TM were identified by proteomic in rat as well as in human skeletal muscles. These three isoforms which are alpha-TM, beta-TM, TPM3, respectively, can be co-expressed in a same fiber indicating that the heterogeneity in the TM dimers is higher than the one described previously. Each isoform displays two distinct spots which could indicate post-translational modifications of TM in skeletal muscle. A transition of TM expression from a slow to a fast phenotype, caracterized by an increase in alpha-TM and a decrease in the beta-TM is measured after HU in soleus muscle. A fast-to-slow transition is observed in human ISA muscles caracterized by an increase in the beta-TM expression. These transitions in TM expression are in accordance with the MHC transitions described previously in these muscles and could be associated with the contractile alterations measured after HU or in ISA muscles.
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