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

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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)30823-30836
Number of pages14
JournalJournal of Biological Chemistry
Volume286
Issue number35
DOIs
StatePublished - Sep 2 2011

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