| A four PDZ domain-containing splice variant form of GRIP1 is localized in GABAergic and glutamatergic synapses in the brain. | |
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MedLine Citation:
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PMID: 15226318 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have isolated, from a rat brain cDNA library, a clone corresponding to a 2779-bp cDNA encoding a novel splice form of the glutamate receptor interacting protein-1 (GRIP1). We call this 696-amino acid splice form GRIP1c 4-7 to differentiate it from longer splice forms of GRIP1a/b containing seven PDZ domains. The four PDZ domains of GRIP1c 4-7 are identical to PDZ domains 4-7 of GRIP1a/b. GRIP1c 4-7 also contains 35 amino acids at the N terminus and 12 amino acids at the C terminus that are different from GRIP1a/b. In transfected HEK293 cells, a majority of GRIP1c 4-7 was associated with the plasma membrane. GRIP1c 4-7 interacted with GluR2/3 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor. In low density hippocampal cultures, GRIP1c 4-7 clusters colocalized with GABAergic (where GABA is gamma-aminobutyric acid) and glutamatergic synapses, although a higher percentage of GRIP1c 4-7 clusters colocalized with gamma-aminobutyric acid, type A, receptor (GABA(A)R) clusters than with alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor clusters. Transfection of hippocampal neurons with hemagglutinin-tagged GRIP1c 4-7 showed that it could target to the postsynaptic complex of GABAergic synapses colocalizing with GABA(A)R clusters. GRIP1c 4-7-specific antibodies, which did not recognize previously described splice forms of GRIP1, recognized a 75-kDa protein that is enriched in a postsynaptic density fraction isolated from rat brain. EM immunocytochemistry experiments showed that in intact brain GRIP1c 4-7 concentrates at postsynaptic complexes of both type I glutamatergic and type II GABAergic synapses although it is also presynaptically localized. These results indicate that GRIP1c 4-7 plays a role not only in glutamatergic synapses but also in GABAergic synapses. |
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Authors:
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Erik I Charych; Wendou Yu; Rongwen Li; David R Serwanski; Celia P Miralles; Xuejing Li; Bih Y Yang; Noelia Pinal; Randall Walikonis; Angel L De Blas |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2004-06-29 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-09-06 Completed Date: 2004-10-19 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 38978-90 Citation Subset: IM |
Affiliation:
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Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AY437398 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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5' Untranslated Regions Alternative Splicing Amino Acid Sequence Animals Brain / metabolism Carrier Proteins / biosynthesis, chemistry* Cell Line Cell Membrane / metabolism DNA, Complementary / metabolism Excitatory Amino Acid Agents / metabolism* GABA Agents / metabolism* Gene Library Golgi Apparatus / metabolism Hippocampus / metabolism Humans Immunoblotting Immunohistochemistry Male Microscopy, Electron Microscopy, Fluorescence Molecular Sequence Data Nerve Tissue Proteins / biosynthesis, chemistry* Neurons / metabolism Precipitin Tests Protein Binding Protein Structure, Tertiary Rats Rats, Sprague-Dawley Receptors, AMPA / biosynthesis, chemistry* Sequence Homology, Amino Acid Synapses / metabolism* Transfection Two-Hybrid System Techniques |
| Grant Support | |
ID/Acronym/Agency:
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NS38752/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/5' Untranslated Regions; 0/Carrier Proteins; 0/DNA, Complementary; 0/Excitatory Amino Acid Agents; 0/GABA Agents; 0/GRIP1 protein, human; 0/Grip1 protein, rat; 0/Nerve Tissue Proteins; 0/Receptors, AMPA |
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