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

Henry LK, Iwamoto H, Field JR, Kaufmann K, Dawson ES, Jacobs MT, Adams C, Felts B, Zdravkovic I, Armstrong V, Combs S, Solis E, Rudnick G, Noskov SY, DeFelice LJ, Meiler J, Blakely RD
J Biol Chem. 2011 286 (35): 30823-36

PMID: 21730057 · PMCID: PMC3162443 · 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.

MeSH Terms (18)

Animals Asparagine Chlorides Cysteine Electrophysiology HeLa Cells Humans Ions Mutagenesis, Site-Directed Neurotransmitter Agents Norepinephrine Oocytes Patch-Clamp Techniques Plasmids Rats Serotonin Serotonin Plasma Membrane Transport Proteins Xenopus laevis

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