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

Details

Serval ID
serval:BIB_A53954E4C3EC
Type
Article: article from journal or magazin.
Collection
Publications
Title
Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.
Journal
Cell reports
Author(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)
Publication state
Published
Issued date
17/10/2017
Peer-reviewed
Oui
Volume
21
Number
3
Pages
679-691
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Keywords
Arc, PSD95, cognition, genetic variants, intellectual disability, schizophrenia, supercomplexes, synaptic complexes, tandem affinity purification
Pubmed
Web of science
Open Access
Yes
Create date
22/11/2017 11:10
Last modification date
20/08/2019 15:10
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