Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival
Authors:
- Elodie HedouEHElodie Hedou
- Sara DouceauSDSara Douceau
- Arnaud ChevilleyACArnaud Chevilley
- Alexandre VarangotAVAlexandre Varangot
- Audrey M. ThiebautATAudrey M. Thiebaut
- Hortense TriniacHTHortense Triniac
- Isabelle BardouIBIsabelle Bardou
- Carine AliCACarine Ali
- Mike MaillassonMMMike Maillasson
- Tiziana CrepaldiTCTiziana Crepaldi
- Paolo ComoglioPCPaolo Comoglio
- Eloïse LemarchandELEloïse Lemarchand
Open Access
- 15 December 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (24) , 13483
Abstract
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.Keywords
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