Activation of cell surface GRP78 decreases endoplasmic reticulum stress and neuronal death

Abstract : The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-related stress conserved pathway that aims to protect cells from being overwhelmed. However, when prolonged, UPR activation converts to a death signal, which relies on its PERK-eIF2α branch. Overactivation of the UPR has been implicated in many neurological diseases, including cerebral ischaemia. Here, by using an in vivo thromboembolic model of stroke on transgenic ER stress-reporter mice and neuronal in vitro models of ischaemia, we demonstrate that ischaemic stress leads to the deleterious activation of the PERK branch of the UPR. Moreover, we show that the serine protease tissue-type plasminogen activator (tPA) can bind to cell surface Grp78 (78 kD glucose-regulated protein), leading to a decrease of the PERK pathway activation, thus a decrease of the deleterious factor CHOP, and finally promotes neuroprotection. Altogether, this work highlights a new role and a therapeutic potential of the chaperone protein Grp78 as a membrane receptor of tPA capable to prevent from ER stress overactivation.
Type de document :
Article dans une revue
Cell Death and Differentiation, Nature Publishing Group, 2017, 24 (9), pp.1518-1529. <10.1038/cdd.2017.35>
Liste complète des métadonnées


http://www.hal.inserm.fr/inserm-01586769
Contributeur : Benoit Roussel <>
Soumis le : mercredi 13 septembre 2017 - 11:32:47
Dernière modification le : jeudi 14 septembre 2017 - 01:09:15

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Citation

Morgane Louessard, Isabelle Bardou, Eloïse Lemarchand, Audrey Thiebaut, Jérôme Parcq, et al.. Activation of cell surface GRP78 decreases endoplasmic reticulum stress and neuronal death. Cell Death and Differentiation, Nature Publishing Group, 2017, 24 (9), pp.1518-1529. <10.1038/cdd.2017.35>. <inserm-01586769>

Partager

Métriques

Consultations de la notice

24