| Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles. | |
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MedLine Citation:
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PMID: 12634427 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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l-Glutamic acid decarboxylase (GAD) exists as both membrane-associated and soluble forms in the mammalian brain. Here, we propose that there is a functional and structural coupling between the synthesis of gamma-aminobutyric acid (GABA) by membrane-associated GAD and its packaging into synaptic vesicles (SVs) by vesicular GABA transporter (VGAT). This notion is supported by the following observations. First, newly synthesized [(3)H]GABA from [(3)H]l-glutamate by membrane-associated GAD is taken up preferentially over preexisting GABA by using immunoaffinity-purified GABAergic SVs. Second, the activity of SV-associated GAD and VGAT seems to be coupled because inhibition of GAD also decreases VGAT activity. Third, VGAT and SV-associated Ca(2+)calmodulin-dependent kinase II have been found to form a protein complex with GAD. A model is also proposed to link the neuronal stimulation to enhanced synthesis and packaging of GABA into SVs. |
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Authors:
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Hong Jin; Heng Wu; Gregory Osterhaus; Jianning Wei; Kathleen Davis; Di Sha; Eric Floor; Che-Chang Hsu; Richard D Kopke; Jang-Yen Wu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2003-03-12 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 100 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2003 Apr |
Date Detail:
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Created Date: 2003-04-02 Completed Date: 2003-05-22 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 4293-8 Citation Subset: IM |
Affiliation:
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Departments of Molecular Biosciences and Medicinal Chemistry, University of Kansas, Lawrence, KS 66045, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Transport Brain / metabolism* Glutamate Decarboxylase / metabolism* Glutamic Acid / isolation & purification, metabolism Kinetics Models, Neurological Rats Rats, Sprague-Dawley Recombinant Fusion Proteins / metabolism Synaptic Vesicles / physiology*, ultrastructure gamma-Aminobutyric Acid / biosynthesis, isolation & purification, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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NS37851/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Recombinant Fusion Proteins; 56-12-2/gamma-Aminobutyric Acid; 56-86-0/Glutamic Acid; EC 4.1.1.15/Glutamate Decarboxylase |
| Comments/Corrections | |
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