Document Detail


A human serotonin transporter mutation causes constitutive activation of transport activity.
MedLine Citation:
PMID:  12869649     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A rarely occurring variant of human serotonin transporter (hSERT) was tested for its functional consequences in HeLa and COS-7 cells. The variant, in which Ile-425 is converted to Val, was significantly different from wild type with respect to its catalytic properties. In both cell types, rates of serotonin (5-HT) transport were higher for the I425V variant. Both an increase in Vmax and a decrease in KM caused this increase in rate. The increase in Vmax was not accounted for by increases in transporter expression or in the distribution of transporter between the cell surface and intracellular pools. The decrease in KM was accompanied by a decrease in the KD for binding of the cocaine analog 2beta-carbomethoxy-3beta-(4-[125I]iodophenyl)tropane. In both HeLa and COS-7 cells, the nitric oxide donor S-nitroso-N-acetylpenicillamine increased the activity of wild-type hSERT to that of the variant but did not change the activity of the I425V variant. This stimulation was prevented by the presence of oxyhemoglobin, which quenches nitric oxide, and by an inhibitor of guanylyl cyclase.
Authors:
Fusun Kilic; Dennis L Murphy; Gary Rudnick
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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.    
Journal Detail:
Title:  Molecular pharmacology     Volume:  64     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-18     Completed Date:  2003-08-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  440-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208066, New Haven, CT 06520-8066, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
Biological Transport / drug effects
Biotinylation
COS Cells
Carrier Proteins / drug effects,  genetics,  metabolism*
Humans
Immunohistochemistry
Isoleucine / genetics
Kinetics
Membrane Glycoproteins / drug effects,  genetics,  metabolism*
Membrane Transport Proteins*
Mutagenesis, Site-Directed
Nerve Tissue Proteins*
Nitric Oxide Donors / pharmacology
Serotonin / metabolism*
Serotonin Plasma Membrane Transport Proteins
Transfection
Valine / genetics
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/Nitric Oxide Donors; 0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins; 50-67-9/Serotonin; 7004-03-7/Valine; 73-32-5/Isoleucine
Comments/Corrections
Comment In:
Mol Pharmacol. 2003 Aug;64(2):196-8   [PMID:  12869622 ]

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


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