Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival.
Int J Mol Sci
; 22(24)2021 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-34948279
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativador de Plasminogênio Tecidual
/
Proteínas Proto-Oncogênicas c-met
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article