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

被引：32

作者：

Henry, L. Keith ^{[1
,4
,9
]}

Iwamoto, Hideki ^{[4
]}

Field, Julie R. ^{[4
]}

Kaufmann, Kristian ^{[5
]}

Dawson, Eric S. ^{[6
,9
,10
]}

Jacobs, Miriam T. ^{[3
]}

Adams, Chelsea

Felts, Bruce

Zdravkovic, Igor ^{[2
]}

Armstrong, Vanessa

Combs, Steven ^{[5
]}

Solis, Ernesto ^{[4
]}

Rudnick, Gary ^{[3
]}

Noskov, Sergei Y. ^{[2
]}

DeFelice, Louis J. ^{[4
,8
]}

Meiler, Jens ^{[4
,5
,9
]}

Blakely, Randy D. ^{[4
,7
,8
]}

机构：

[1] Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58203 USA

[2] Univ Calgary, Dept Biol Sci, Inst Biocomplex & Informat, Calgary, AB T2N 1N4, Canada

[3] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

[4] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA

[5] Vanderbilt Univ, Sch Med, Dept Chem, Nashville, TN 37232 USA

[6] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA

[7] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37232 USA

[8] Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Nashville, TN 37232 USA

[9] Vanderbilt Univ, Sch Med, Struct Biol Ctr, Nashville, TN 37232 USA

[10] Vanderbilt Univ, Sch Med, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 35期

关键词：

AMINO-ACID TRANSPORTER; DOPAMINE TRANSPORTER; DOMAIN-I; MOLECULAR-MECHANISM; ALTERNATING ACCESS; SIDE-CHAIN; RAT-BRAIN; SUBSTRATE RECOGNITION; SCANNING MUTAGENESIS; PERMEATION PATHWAY;

D O I：

10.1074/jbc.M111.250308

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：30823 / 30836

页数：14

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