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

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.

SUBMITTER: Henry LK 

PROVIDER: S-EPMC3162443 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

Henry L Keith LK   Iwamoto Hideki H   Field Julie R JR   Kaufmann Kristian K   Dawson Eric S ES   Jacobs Miriam T MT   Adams Chelsea C   Felts Bruce B   Zdravkovic Igor I   Armstrong Vanessa V   Combs Steven S   Solis Ernesto E   Rudnick Gary G   Noskov Sergei Y SY   DeFelice Louis J LJ   Meiler Jens J   Blakely Randy D RD  

The Journal of biological chemistry 20110705 35

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, an  ...[more]

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