Fernández, E, Collins, MO, Frank, RAW orcid.org/0000-0001-9724-9547 et al. (20 more authors) (2017) Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence. Cell Reports, 21 (3). pp. 679-691. ISSN 2211-1247
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | tandem affinity purification; PSD95; Arcsynaptic complexes; supercomplexes; genetic variants; cognition; intellectual disability; schizophrenia |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Oct 2018 14:48 |
Last Modified: | 09 Oct 2018 14:48 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.celrep.2017.09.045 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:135835 |