Document Detail


Molecular physiology of norepinephrine and serotonin transporters.
MedLine Citation:
PMID:  7823027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cocaine- and antidepressant-sensitive norepinephrine and serotonin transporters (NETs and SERTs) are closely related members of the Na+/Cl- transporter gene family, whose other members include transporters for inhibitory amino acid transmitters, neuromodulators, osmolytes and nutrients. Availability of cloned NET and SERT cDNAs has permitted rapid progress in the definition of cellular sites of gene expression, the generation of transporter-specific antibodies suitable for biosynthetic and localization studies, the examination of structure-function relationships in heterologous expression systems and a biophysical analysis of transporter function. In situ hybridization and immunocytochemical studies indicate a primary expression of NET and SERT genes in brain by noradrenergic and serotonergic neurons, respectively. Both NET and SERT are synthesized as glycoproteins, with multiple glycosylation states apparent for SERT proteins in the brain and periphery. N-glycosylation of NET and SERT appears to be essential for transporter assembly and surface expression, but not for antagonist binding affinity. Homology cloning efforts have revealed novel NET and SERT homologs in nonmammalian species that are of potential value in the delineation of the precise sites for substrate and antagonist recognition, including a Drosophila melanogaster SERT with NET-like pharmacology. Electrophysiological recording of human NETs and SERTs stably expressed in HEK-293 cells reveals that both transporters move charge across the plasma membrane following the addition of substrates; these currents can be blocked by NET-and SERT-selective antagonists as well as by cocaine.
Authors:
R D Blakely; L J De Felice; H C Hartzell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; 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:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0243705     Medline TA:  J Exp Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  263-81     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / physiology*
Carrier Proteins / biosynthesis*,  chemistry,  genetics
Cell Line
Chromosome Mapping
Chromosomes, Human, Pair 17
Cloning, Molecular
Drosophila Proteins
Drosophila melanogaster / physiology
Humans
Membrane Glycoproteins / biosynthesis*,  chemistry,  genetics
Membrane Transport Proteins*
Nerve Tissue Proteins / biosynthesis
Neurons / physiology*
Norepinephrine / metabolism
Norepinephrine Plasma Membrane Transport Proteins
Protein Structure, Secondary
Serotonin / metabolism
Serotonin Plasma Membrane Transport Proteins
Symporters*
Grant Support
ID/Acronym/Agency:
DA07390/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Drosophila Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/Norepinephrine Plasma Membrane Transport Proteins; 0/SLC6A2 protein, human; 0/SLC6A4 protein, human; 0/SerT protein, Drosophila; 0/Serotonin Plasma Membrane Transport Proteins; 0/Symporters; 50-67-9/Serotonin; 51-41-2/Norepinephrine

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


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