Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.

Détails

ID Serval
serval:BIB_A53954E4C3EC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.
Périodique
Cell reports
Auteur⸱e⸱s
Fernández E., Collins M.O., Frank RAW, Zhu F., Kopanitsa M.V., Nithianantharajah J., Lemprière S.A., Fricker D., Elsegood K.A., McLaughlin C.L., Croning MDR, Mclean C., Armstrong J.D., Hill W.D., Deary I.J., Cencelli G., Bagni C., Fromer M., Purcell S.M., Pocklington A.J., Choudhary J.S., Komiyama N.H., Grant SGN
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
17/10/2017
Peer-reviewed
Oui
Volume
21
Numéro
3
Pages
679-691
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia, intellectual disability, autism, and epilepsy mutations and normal variants in intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect human cognitive function.

Mots-clé
Arc, PSD95, cognition, genetic variants, intellectual disability, schizophrenia, supercomplexes, synaptic complexes, tandem affinity purification
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/11/2017 12:10
Dernière modification de la notice
20/08/2019 16:10
Données d'usage