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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2011-3-23
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pubmed:abstractText |
Glutamate receptor interacting protein 1 (GRIP1) is a neuronal scaffolding protein that interacts directly with the C termini of glutamate receptors 2/3 (GluA2/3) via its PDZ domains 4 to 6 (PDZ4-6). We found an association (P<0.05) of a SNP within the PDZ4-6 genomic region with autism by genotyping autistic patients (n=480) and matched controls (n=480). Parallel sequencing identified five rare missense variants within or near PDZ4-6 only in the autism cohort, resulting in a higher cumulative mutation load (P=0.032). Two variants correlated with a more severe deficit in reciprocal social interaction in affected sibling pairs from proband families. These variants were associated with altered interactions with GluA2/3 and faster recycling and increased surface distribution of GluA2 in neurons, suggesting gain-of-function because GRIP1/2 deficiency showed opposite phenotypes. Grip1/2 knockout mice exhibited increased sociability and impaired prepulse inhibition. These results support a role for GRIP in social behavior and implicate GRIP1 variants in modulating autistic phenotype.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GRIP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Grip1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Grip1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Grip2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glutamate
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:AdamczykAbbyA,
pubmed-author:AnggonoVictorV,
pubmed-author:FallinM DanieleMD,
pubmed-author:HuganirRichard LRL,
pubmed-author:KaufmannWalterW,
pubmed-author:MejiasRebecaR,
pubmed-author:NiranjanTejasviT,
pubmed-author:PletnikovMikhailM,
pubmed-author:SchwartzCharles ECE,
pubmed-author:SharmaKamalK,
pubmed-author:SkinnerCindyC,
pubmed-author:StevensonRoger ERE,
pubmed-author:ThomasGareth MGM,
pubmed-author:ValleDavidD,
pubmed-author:WangTaoT
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4920-5
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pubmed:dateRevised |
2011-9-23
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pubmed:meshHeading |
pubmed-meshheading:21383172-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21383172-Animals,
pubmed-meshheading:21383172-Autistic Disorder,
pubmed-meshheading:21383172-Carrier Proteins,
pubmed-meshheading:21383172-Cells, Cultured,
pubmed-meshheading:21383172-Child,
pubmed-meshheading:21383172-Cohort Studies,
pubmed-meshheading:21383172-Humans,
pubmed-meshheading:21383172-Male,
pubmed-meshheading:21383172-Mice,
pubmed-meshheading:21383172-Mice, Knockout,
pubmed-meshheading:21383172-Mutation, Missense,
pubmed-meshheading:21383172-Nerve Tissue Proteins,
pubmed-meshheading:21383172-Neurons,
pubmed-meshheading:21383172-Polymorphism, Single Nucleotide,
pubmed-meshheading:21383172-Protein Structure, Tertiary,
pubmed-meshheading:21383172-Rats,
pubmed-meshheading:21383172-Receptors, Glutamate
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pubmed:year |
2011
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pubmed:articleTitle |
Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism.
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pubmed:affiliation |
McKusick-Nathans Institute of Genetic Medicine and Department of Pediatrics, The Howard Hughes Medical Institute, Predoctoral Training Program in Human Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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