A Conserved Asparagine Residue in Transmembrane Segment 1 (TM1) of Serotonin Transporter Dictates Chloride-coupled Neurotransmitter Transport

作者：Henry L Keith^*; Iwamoto Hideki; Field Julie R; Kaufmann Kristian; Dawson Eric S; Jacobs Miriam T; Adams Chelsea; Felts Bruce; Zdravkovic Igor; Armstrong Vanessa; Combs Steven; Solis Ernesto; Rudnick Gary; Noskov Sergei Y; DeFelice Louis J; Meiler Jens; Blakely Randy D

来源：Journal of Biological Chemistry, 2011, 286(35): 30823-30836.

DOI：10.1074/jbc.M111.250308

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.

• 出版日期2011-9-2