Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

Vincenzo Salpietro 1, 2, 3 Christine Dixon 1 Hui Guo 4 Oscar Bello 5 Jana Vandrovcova 6 Stephanie Efthymiou 7 Reza Maroofian 8 Gali Heimer 9 Lydie Burglen 10 Stephanie Valence 11 Erin Torti 12 Moritz Hacke 13 Julia Rankin 14 Huma Tariq 1 Estelle Colin 15, 16 Vincent Procaccio 15, 16 Pasquale Striano 17 Kshitij Mankad 18 Andreas Lieb 1 Sharon Chen 19 Laura Pisani 20 Conceição Bettencourt 1 Roope Männikkö 1 Andreea Manole 1 Alfredo Brusco 21 Enrico Grosso 21 Giovanni Battista Ferrero 21 Judith Armstrong-Moron 22 Sophie Gueden 16 Omer Bar-Yosef 23 Michal Tzadok 23 Kristin Monaghan 12 Teresa Santiago-Sim 12 Richard Person 12 Megan Cho 12 Rebecca Willaert 12 Yongjin Yoo 24 Jong-Hee Chae 24 Yingting Quan 25 Huidan Wu 25 Tianyun Wang 25 Raphael Bernier 4 Kun Xia 25 Alyssa Blesson 26 Mahim Jain 26 Mohammad Motazacker 27 Bregje Jaeger 27 Amy Schneider 28 Katja Boysen 28 Alison Muir 4 Candace Myers 4 Ralitza Gavrilova 29 Lauren Gunderson 29 Laura Schultz-Rogers 29 Eric Klee 30 David Dyment 31 Matthew Osmond 32 Mara Parellada 33 Cloe Llorente 33 Javier Gonzalez-Peñas 33 Angel Carracedo 34 Arie van Haeringen 35 Claudia Ruivenkamp 35 Caroline Nava 36 Delphine Héron 37 Rosaria Nardello 38 Michele Iacomino 17 Carlo Minetti 17 Aldo Skabar 39 Antonella Fabretto 39 Miquel Raspall-Chaure 40 Michael Chez 41 Anne Tsai 42 Emily Fassi 43 Marwan Shinawi 44 John Constantino 45 Rita de Zorzi 46 Sara Fortuna 39 Fernando Kok 47 Boris Keren 48 Dominique Bonneau 49 Murim Choi 50 Bruria Benzeev 23 Federico Zara 51 Heather Mefford 4 Ingrid Scheffer 28 Jill Clayton-Smith 52 Alfons Macaya 40 James Rothman 53 Evan Eichler 4 Dimitri Kullmann 1 Henry Houlden 1 Yves Dauvilliers 54
Abstract : AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.
Liste complète des métadonnées

https://hal.umontpellier.fr/hal-02577355
Contributeur : Nathalie Salvy-Cordoba <>
Soumis le : jeudi 14 mai 2020 - 18:17:14
Dernière modification le : mercredi 14 octobre 2020 - 04:18:13

Lien texte intégral

Identifiants

Citation

Vincenzo Salpietro, Christine Dixon, Hui Guo, Oscar Bello, Jana Vandrovcova, et al.. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Nature Communications, Nature Publishing Group, 2019, 10 (1), ⟨10.1038/s41467-019-10910-w⟩. ⟨hal-02577355⟩

Partager

Métriques

Consultations de la notice

69