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Endogenous brain ARC complexes

ABSTRACT: Arc is an activity regulated neuronal protein yet little is known about its protein interactions, assembly into multiprotein complexes, role in human disease and cognition. We applied an integrated proteomic and genetic strategy using targeted tagging of a Tandem Affinity Purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice, biochemical and proteomic characterization of native complexes in wild type and knockout mice, and human genetic analyses of disease and intelligence. TAP tagging enabled efficient purification of complexes and identification of many novel Arcinteracting 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 postsynaptic Arc- PSD95 complexes are enriched in schizophrenia, intellectual disability, autism and epilepsy mutations and normal variants in intelligence. Arc-PSD95 postsynaptic complexes are a molecular substrate for the convergence of normal and pathological genetic variants impacting on human cognitive function.

INSTRUMENT(S): LTQ FT

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Mark Collins

LAB HEAD: Mark Collins

PROVIDER: PXD007283 | Pride | 2017-10-19

REPOSITORIES: Pride

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			Action	DRS
	ARC02_2009Aug13-1.RAW	Raw
	ARC02_2009Aug13-10.RAW	Raw
	ARC02_2009Aug13-11.RAW	Raw
	ARC02_2009Aug13-12.RAW	Raw
	ARC02_2009Aug13-2.RAW	Raw

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