Title :

Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion

Author(s) :

Capuz, Alice [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Osien, Sylvain [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Karnoub, Melodie-Anne [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Aboulouard, Soulaimane [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Laurent, Estelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Coyaud, Etienne-Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Raffo Romero, Antonella [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Duhamel, Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Bonnefond, Amélie [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Derhourhi, Mehdi [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Trerotola, Marco [Auteur]
Università degli studi "G. d'Annunzio" Chieti-Pescara [Chieti-Pescara] [Ud'A]
Belkoura, Ikram [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Zilkova, Monika [Auteur]
Slovak Academy of Sciences [SAS]
Kobeissy, Firas [Auteur]
American University of Beirut [Beyrouth] [AUB]
Vanden Abeele, Fabien [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
Fournier, Isabelle [Auteur]
Institut universitaire de France [IUF]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Cizkova, Dasa [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
University of Veterinary Medicine and Pharmacy [Košice, Slovakia]
Slovak Academy of Sciences [SAS]
Rodet, Franck [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Institut universitaire de France [IUF]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Journal title :

Cell Death and Disease

Abbreviated title :

Cell Death Dis

Volume number :

14

Pages :

237

Publisher :

Nature Publishing Group

Publication date :

2023-04-04

ISSN :

2041-4889

HAL domain(s) :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

English abstract : [en]

Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains ...
Show more >Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains as well as light chains. However, their edification is different from the ones found in B cells and they resemble aberrant immunoglobulins observed in several cancers. Moreover, the complete enzymatic V(D)J recombination complex has also been identified in astrocytes. In addition, the constant heavy chain is also present in adult rat astrocytes, whereas in primary astrocytes from human fetus we identified constant and variable kappa chains as well as the substitution lambda chains known to be involved in pre-B cells. To gather insights into the function of these neural IgGs, CRISPR-Cas9 of IgG2B constant heavy chain encoding gene (Igh6), IgG2B overexpression, proximal labeling of rat astrocytes IgG2B and targets identification through 2D gels were performed. In Igh6 KO astrocytes, overrepresentation of factors involved in hematopoietic cells, neural stem cells, and the regulation of neuritogenesis have been identified. Moreover, overexpression of IgG2B in astrocytes induces the CRTC1-CREB-BDNF signaling pathway known to be involved in gliogenesis, whereas Igh6 KO triggers the BMP/YAP1/TEAD3 pathway activated in astrocytes dedifferentiation into neural progenitors. Proximal labeling experiments revealed that IgG2B is N-glycosylated by the OST complex, addressed to vesicle membranes containing the ATPase complex, and behaves partially like CD98hc through its association with LAT1. These experiments also suggest that proximal IgG2B-LAT1 interaction occurs concomitantly with MACO-1 and C2CD2L, at the heart of a potentially novel cell signaling platform. Finally, we demonstrated that these chains are synthesized individually and associated to recognize specific targets. Indeed, intermediate filaments Eif4a2 and Pdia6 involved in astrocyte fate constitute targets for these neural IgGs. Taken together, we hypothese that neural aberrant IgG chains may act as gatekeepers of astrocytes' fate.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

ANR Project :

Plate forme Lilloise de séquençage du génome humain pour une médecine personnalisée
Organisation et montée en puissance d'une Infrastructure Nationale de Génomique

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Physiologie Cellulaire (PHYCELL) - U1003
• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Troubles cognitifs dégénératifs et vasculaires

Submission date :

2023-11-08T12:52:52Z
2023-11-09T18:00:53Z
2023-11-10T14:46:56Z