Document Detail


GABA transporters in Drosophila melanogaster: molecular cloning, behavior, and physiology.
MedLine Citation:
PMID:  10212397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular cloning of GABA transporter-homologous cDNAs from a Drosophila melanogaster head-specific library was accomplished using a conserved oligomer from a highly conserved domain within the mammalian GABA transporters. Partial DNA sequencing of these cDNAs demonstrated homology with the mammalian transporters, indicating these are ancient, evolutionarily conserved molecules. Although the Drosophila cDNAs had distinct restriction enzyme patterns, they recognized the same locus in Drosophila genomic DNA, suggesting that the multiple isoforms might arise via alternative splicing. Antibodies specific for the mammalian GABA transporters GAT 1, GAT 2 and GAT 3 recognized non-overlapping and developmentally distinct patterns of expression in Drosophila neuronal tissues. Treatment of larval instars with nipecotic acid, a generalized GABA reuptake inhibitor, revealed specific, dose-dependent alterations in behavior consistent with the presence of multiple transporter molecules with differing affinities for this drug. Synaptic current recordings revealed that nipecotic acid treated larvae have an increase in latency jitter of evoked quantal release, resulting in a broader average excitatory junctional current which was manifested in a broader EJP. These results imply that alterations in the development of the CNS occur if GABAergic neurotransmission is potentiated during development. The data suggest that, as in mammals, there are multiple GABA transporters in Drosophila whose expression is differentially regulated.
Authors:
W S Neckameyer; R L Cooper
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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.    
Journal Detail:
Title:  Invertebrate neuroscience : IN     Volume:  3     ISSN:  1354-2516     ISO Abbreviation:  Invert. Neurosci.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1999-05-25     Completed Date:  1999-05-25     Revised Date:  2006-11-20    
Medline Journal Info:
Nlm Unique ID:  9602489     Medline TA:  Invert Neurosci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  279-94     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Physiological Sciences, St. Louis University School of Medicine, MO 63104, USA. NECKAMWS@SLU.EDU
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Analysis of Variance
Animals
Blotting, Southern
Carrier Proteins / genetics,  physiology*
Cloning, Molecular
Conserved Sequence
DNA, Complementary / isolation & purification*
Drosophila melanogaster
Evolution, Molecular
GABA Plasma Membrane Transport Proteins
Membrane Proteins / genetics,  physiology*
Membrane Transport Proteins*
Molecular Sequence Data
Nerve Tissue Proteins / genetics,  physiology*
Organic Anion Transporters*
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Synaptic Transmission
gamma-Aminobutyric Acid / metabolism*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/DNA, Complementary; 0/GABA Plasma Membrane Transport Proteins; 0/Membrane Proteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/Organic Anion Transporters; 56-12-2/gamma-Aminobutyric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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