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Journal articles
Activation of cell surface GRP78 decreases endoplasmic reticulum stress and neuronal death
Morgane Louessard
1
Isabelle Bardou
1
Eloïse Lemarchand
1
Audrey Thiebaut
1
Jérôme Parcq
1
Jérôme Leprince
2, 3
Anne Terrisse
4
Valérie Carraro
4
Pierre Fafournoux
4
Alain Bruhat
4
Cyrille Orset
1
Denis Vivien
1, 5
Carine Ali
1
Benoit Roussel
1, *
*
Corresponding author
Morgane D Louessard 1
Author
Isabelle D Bardou 1
Author
Eloïse D Lemarchand 1
Author
Audrey D Thiebaut 1
Author
Jérôme D Parcq 1
Author
Jérôme D Leprince 2, 3
Author
Anne M Terrisse 4
Author
Valérie M Carraro 4
Author
Pierre M Fafournoux 4
Author
Alain Bruhat 4
Author Employer institution : Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement IdHAL : alain-bruhat
Cyrille D Orset 1
Author
Denis D Vivien 1, 5
Author
Carine D Ali 1
Author
Benoit D Roussel 1
Correspondent author IdHAL : benoit-roussel ORCID : https://orcid.org/0000-0003-0575-8112
1
Sérine protéases et physiopathologie de l'unité neurovasculaire (Campus Jules Horowitz - Boulevard Henri Becquerel - BP 5229 - 14074 CAEN Cedex 5. - France)
- UNICAEN - Université de Caen Normandie (Esplanade de la Paix - CS 14032 - 14032 CAEN Cedex 5 - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U919 (101, rue de Tolbiac, 75013 Paris - France)
2
DC2N - Différenciation et communication neuronale et neuroendocrine (Place Emile Blondel Faculté des Sciences et Techniques 76821 Mont-Saint-Aignan Cedex - France)
- UNIROUEN - Université de Rouen Normandie : U982 (1, rue Thomas Becket 76821 Mont-Saint-Aignan Cedex - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U982 (101, rue de Tolbiac, 75013 Paris - France)
3
PRIMACEN - Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (Faculté des Sciences et Techniques Place Emile Blondel 76821 Mont-Saint-Aignan Cedex - France)
- UNIROUEN - Université de Rouen Normandie (1, rue Thomas Becket 76821 Mont-Saint-Aignan Cedex - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
- IRIB - Institute for Research and Innovation in Biomedicine (22 Boulevard Gambetta
76183 Rouen Cedex - France)
- UNIROUEN - Université de Rouen Normandie : FED 4220 (1, rue Thomas Becket 76821 Mont-Saint-Aignan Cedex - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
- CNRS - Centre National de la Recherche Scientifique (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : FED 4220 (101, rue de Tolbiac, 75013 Paris - France)
- UNIROUEN - Université de Rouen Normandie : FED 4220 (1, rue Thomas Becket 76821 Mont-Saint-Aignan Cedex - France)
4
UNH - Unité de Nutrition Humaine (Site INRAE Theix : 63122 Saint-Gènes-Champanelle // Site Clermont : UFR de Médecine et de Pharmacie, TSA 50400, 28 Place Henri Dunant, 63001 Clermont-Ferrand - France)
- INRA - Institut National de la Recherche Agronomique : UMR1019 (France)
- UCA [2017-2020] - Université Clermont Auvergne [2017-2020] : UMR1019 (49, bd François-Mitterrand / CS 60032 / 63001 Clermont-Ferrand Cedex 1 - France)
5
UBRC - Unité de Biostatistique et de Recherche Clinique (CHU de Caen - avenue de la Côte de Nacre 14000 Caen - France)
- UNICAEN - Université de Caen Normandie (Esplanade de la Paix - CS 14032 - 14032 CAEN Cedex 5 - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
- CHU Caen (Avenue de la Côte de Nacre 14000 Caen - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
- TCBN - Tumorothèque de Caen Basse-Normandie (3 avenue du Général Harris 14076 Caen cedex 5 - France)
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.
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Journal articles
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https://www.hal.inserm.fr/inserm-01586769
Contributor : Benoit Roussel Connect in order to contact the contributor
Submitted on : Wednesday, September 13, 2017 - 11:32:47 AM
Last modification on : Saturday, June 19, 2021 - 3:20:13 AM
Long-term archiving on: : Thursday, December 14, 2017 - 12:39:27 PM
Contributor : Benoit Roussel Connect in order to contact the contributor
Submitted on : Wednesday, September 13, 2017 - 11:32:47 AM
Last modification on : Saturday, June 19, 2021 - 3:20:13 AM
Long-term archiving on: : Thursday, December 14, 2017 - 12:39:27 PM
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- HAL Id : inserm-01586769, version 1
- DOI : 10.1038/cdd.2017.35
- PUBMED : 28644439
- PUBMEDCENTRAL : PMC5563983
- PRODINRA : 398716
- WOS : 000407506500007
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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⟩
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