Résumé :
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The plasminogen activation (PA) system is a group of serine proteases that participate in tissue remodeling by degrading most of components of the extracellular matrix. Different studies have shown that PA system components (plasminogen and urokinase-plasminogen activator) play a role in myogenesis in vitro and in muscle regeneration in vivo. Alpha-enolase constitutes a receptor for plasminogen in several cell types, where it acts focalizing proteolytic activity on the cell surface. We have previously shown that alpha-enolase/plasminogen binding is required for myogenic differentiation, fusion, migration and invasion processes, in an in vitro model of myogenesis. Moreover, the blockage of alpha-enolase/plasminogen binding in an animal model of muscle regeneration impairs the regeneration process, indicating an important role of cell surface-associated plasminogen, in an alpha-enolase-dependent way. In the last years, evidences have appeared showing that plasmin(ogen) induces an intracellular response after binding to cell surface in several cell types, but it has never been evaluated in myogenic cells. We have analysed the intracellular signalling response of plasminogen binding in myoblasts C2C12 and in primary cultures of Muscle Precursor Cells (MPCs). Our results showed that plasmin(ogen) induces PI3K/AKT and MEK/ERK phosphorylation in C2C12 myoblasts and in MPCs. This activation is alpha-enolase/plasmin(ogen) binding-dependent because inhibitors of plasminogen-cell surface binding (as MAb11G1 and EACA) abrogates this activation. Plasminogen induced invasion and migration were also inhibited by MAb11G1 and EACA, suggesting an important role for alpha-enolase/plasminogen binding induced response in these processes. As alpha-enolase lacks a transmembrane or intracellular domain, it is presumed to act through association with other membrane proteins. Experiments are being performed to identify such molecular partner that could collaborate with alpha-enolase to transduce plasmin(ogen)-induced intracellular signalling. To our knowledge, the role of alpha-enolase as a mediator of plasminogen-induced intracellular signalling in myogenic cells is demonstrated for the first time.
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