Document Detail


Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles.
MedLine Citation:
PMID:  12634427     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
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:
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:
Created Date:  2003-04-02     Completed Date:  2003-05-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4293-8     Citation Subset:  IM    
Affiliation:
Departments of Molecular Biosciences and Medicinal Chemistry, University of Kansas, Lawrence, KS 66045, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
NS37851/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
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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