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Article Dans Une Revue International Journal of Molecular Sciences Année : 2021

Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival

Tiziana Crepaldi
Paolo Comoglio

Résumé

Tissue-type plasminogen activator (tPA) plays roles in the development and the plasticity of the nervous system. Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of N-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. Thus, our present study unmasks a new mechanism of action of tPA, with its two-chains form mediating a crosstalk between MET and the GluN2B subunit of NMDARs to control neuronal survival.

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Cancer
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Dates et versions

inserm-03547069 , version 1 (28-01-2022)

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Elodie Hedou, Sara Douceau, Arnaud Chevilley, Alexandre Varangot, Audrey Thiebaut, et al.. Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival. International Journal of Molecular Sciences, 2021, 22 (24), pp.13483. ⟨10.3390/ijms222413483⟩. ⟨inserm-03547069⟩
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