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J Biol Chem. 2011 Sep 2;286(35):30823-36. doi: 10.1074/jbc.M111.250308. Epub 2011 Jul 5.

A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport.

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1
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8548, USA. keith.henry@med.und.edu

Abstract

Na(+)- and Cl(-)-dependent uptake of neurotransmitters via transporters of the SLC6 family, including the human serotonin transporter (SLC6A4), is critical for efficient synaptic transmission. Although residues in the human serotonin transporter involved in direct Cl(-) coordination of human serotonin transport have been identified, the role of Cl(-) in the transport mechanism remains unclear. Through a combination of mutagenesis, chemical modification, substrate and charge flux measurements, and molecular modeling studies, we reveal an unexpected role for the highly conserved transmembrane segment 1 residue Asn-101 in coupling Cl(-) binding to concentrative neurotransmitter uptake.

PMID:
21730057
PMCID:
PMC3162443
DOI:
10.1074/jbc.M111.250308
[Indexed for MEDLINE]
Free PMC Article
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