Document Detail

Structure, function and brain localization of neurotransmitter transporters.
MedLine Citation:
PMID:  7823028     Owner:  NLM     Status:  MEDLINE    
We studied four different cDNAs encoding GABA transporters and three different cDNAs encoding glycine transporters in mouse and rat brains. A genomic clone of two of the glycine transporters (GLYT1a and GLYT1b) revealed that they derive from differential splicing of a single gene. The third glycine transporter (GLYT2) is encoded by a separate gene. Antibodies were raised against seven of these neurotransmitter transporters and their cytochemical localization in the mouse brain was studied. In general, we observed a deviation from the classical separation of neuronal and glial transporters. It seems that each of the neurotransmitter transporters is present in specific places in the brain and is expressed in a different way in very specific areas. For example, the GABA transporter GAT4, which also transports beta-alanine, was localized to neurons. However, GAT1, which is specific for GABA, was localized not only to neurons but also to glial cells. The recently discovered glycine transporter GLYT2 was of particular interest because of its deviation from the general structure by a very extended N terminus containing multiple potential phosphorylation sites. Western analysis and immunocytochemistry in frozen sections of mouse brain demonstrated a clear caudal-rostral gradient of GLYT2 distribution, with massive accumulation in the spinal cord and brainstem and less in the cerebellum. Its distribution is typically neuronal and it is present in processes with varicosities. A correlation as observed between the pattern we obtained and that observed previously from strychnine binding studies. The results indicate that GLYT2 is involved in the termination of glycine neurotransmission at the classical inhibitory system in the hindbrain. The availability of four different GABA transporters made it possible to look for specific binding sites upon the neurotransmitter transporters. An extensive program of site-directed mutagenesis led us to identify a potential neurotransmitter binding site on the GABA transporters.
F Jursky; S Tamura; A Tamura; S Mandiyan; H Nelson; N Nelson
Related Documents :
10980488 - Postnatal maturation of gephyrin/glycine receptor clusters on developing renshaw cells.
8795618 - The regulation of heme turnover and carbon monoxide biosynthesis in cultured primary ra...
20164358 - Structural determinants of d-cycloserine efficacy at the nr1/nr2c nmda receptors.
1347648 - In vivo modulation of n-methyl-d-aspartate receptor-dependent long-term potentiation by...
10051758 - Presynaptic gabaergic control of the locomotor drive in the isolated spinal cord of neo...
20039908 - Role of endothelin in the effects of isoprenaline on potassium currents and calsequestr...
Publication Detail:
Type:  Comparative Study; Journal Article; Review    
Journal Detail:
Title:  The Journal of experimental biology     Volume:  196     ISSN:  0022-0949     ISO Abbreviation:  J. Exp. Biol.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1995-02-16     Completed Date:  1995-02-16     Revised Date:  2006-11-20    
Medline Journal Info:
Nlm Unique ID:  0243705     Medline TA:  J Exp Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  283-95     Citation Subset:  IM    
Roche Institute of Molecular Biology, Nutley, NJ 07110.
Data Bank Information
Bank Name/Acc. No.:
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Sequence
Amino Acid Transport Systems, Neutral*
Brain / cytology,  metabolism,  physiology*
Carrier Proteins / biosynthesis*,  chemistry,  physiology
GABA Plasma Membrane Transport Proteins
Glycine / metabolism
Glycine Plasma Membrane Transport Proteins
Membrane Proteins / biosynthesis*,  chemistry,  physiology
Membrane Transport Proteins*
Molecular Sequence Data
Organic Anion Transporters*
Sequence Homology, Amino Acid
gamma-Aminobutyric Acid / metabolism
Reg. No./Substance:
0/Amino Acid Transport Systems, Neutral; 0/Carrier Proteins; 0/GABA Plasma Membrane Transport Proteins; 0/Glycine Plasma Membrane Transport Proteins; 0/Membrane Proteins; 0/Membrane Transport Proteins; 0/Organic Anion Transporters; 0/SLC6A1 protein, human; 0/SLC6A5 protein, human; 0/Slc6a1 protein, mouse; 0/Slc6a1 protein, rat; 0/Slc6a5 protein, mouse; 0/Slc6a5 protein, rat; 56-12-2/gamma-Aminobutyric Acid; 56-40-6/Glycine

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

Previous Document:  Molecular physiology of norepinephrine and serotonin transporters.
Next Document:  Special transport and neurological significance of two amino acids in a configuration conventionally...