Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter.
Barker EL, Moore KR, Rakhshan F, Blakely RD.
???displayArticle.abstract???
Mutation of a conserved Asp (D98) in the rat serotonin (5HT) transporter (rSERT) to Glu (D98E) led to decreased 5HT transport capacity, diminished coupling to extracellular Na+ and Cl-, and a selective loss of antagonist potencies (cocaine, imipramine, and citalopram but not paroxetine or mazindol) with no change in 5HT Km value. D98E, which extends the acidic side chain by one carbon, affected the rank-order potency of substrate analogs for inhibition of 5HT transport, selectively increasing the potency of two analogs with shorter alkylamine side chains, gramine, and dihydroxybenzylamine. D98E also increased the efficacy of gramine relative to 5HT for inducing substrate-activated currents in Xenopus laevis oocytes, but these currents were noticeably dependent on extracellular medium acidification. I-V profiles for substrate-independent and -dependent currents indicated that the mutation selectively impacts ion permeation coupled to 5HT occupancy. The ability of the D98E mutant to modulate selective aspects of substrate recognition, to perturb ion dependence as well as modify substrate-induced currents, suggests that transmembrane domain I plays a critical role in defining the permeation pathway of biogenic amine transporters.
Akabas,
Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
1992,
Pubmed
,
Xenbase Barker,
Chimeric human and rat serotonin transporters reveal domains involved in recognition of transporter ligands.
1994,
Pubmed Barker,
Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter.
1996,
Pubmed Barker,
High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol.
1998,
Pubmed Bennett,
The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid transporter from rat brain.
1997,
Pubmed Blakely,
Cloning and expression of a functional serotonin transporter from rat brain.
1991,
Pubmed Blakely,
Vaccinia-T7 RNA polymerase expression system: evaluation for the expression cloning of plasma membrane transporters.
1991,
Pubmed Boja,
High-affinity binding of [125I]RTI-55 to dopamine and serotonin transporters in rat brain.
1992,
Pubmed Buck,
Chimeric dopamine-norepinephrine transporters delineate structural domains influencing selectivity for catecholamines and 1-methyl-4-phenylpyridinium.
1994,
Pubmed Cao,
H+ permeation and pH regulation at a mammalian serotonin transporter.
1997,
Pubmed
,
Xenbase Cao,
Amino acid residues that control pH modulation of transport-associated current in mammalian serotonin transporters.
1998,
Pubmed
,
Xenbase Chen,
Determination of external loop topology in the serotonin transporter by site-directed chemical labeling.
1998,
Pubmed Chen,
External cysteine residues in the serotonin transporter.
1997,
Pubmed Chen,
The third transmembrane domain of the serotonin transporter contains residues associated with substrate and cocaine binding.
1997,
Pubmed Cheng,
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
1973,
Pubmed Clark,
Analysis of the transmembrane topology and membrane assembly of the GAT-1 gamma-aminobutyric acid transporter.
1997,
Pubmed
,
Xenbase Ferrer,
Cocaine alters the accessibility of endogenous cysteines in putative extracellular and intracellular loops of the human dopamine transporter.
1998,
Pubmed Fuerst,
Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase.
1986,
Pubmed Galli,
Drosophila serotonin transporters have voltage-dependent uptake coupled to a serotonin-gated ion channel.
1997,
Pubmed
,
Xenbase Galli,
Norepinephrine transporters have channel modes of conduction.
1996,
Pubmed Galli,
Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants.
1995,
Pubmed Graham,
A common binding site for tricyclic and nontricyclic 5-hydroxytryptamine uptake inhibitors at the substrate recognition site of the neuronal sodium-dependent 5-hydroxytryptamine transporter.
1989,
Pubmed Gu,
Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence.
1994,
Pubmed Humphreys,
Ligand binding to the serotonin transporter: equilibria, kinetics, and ion dependence.
1994,
Pubmed Kitayama,
Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding.
1992,
Pubmed Kunkel,
Rapid and efficient site-specific mutagenesis without phenotypic selection.
1987,
Pubmed Lester,
Listening to neurotransmitter transporters.
1996,
Pubmed Lin,
Single-channel currents produced by the serotonin transporter and analysis of a mutation affecting ion permeation.
1996,
Pubmed
,
Xenbase Mager,
Conducting states of a mammalian serotonin transporter.
1994,
Pubmed
,
Xenbase Mager,
Ion binding and permeation at the GABA transporter GAT1.
1996,
Pubmed
,
Xenbase Melikian,
Inability to N-glycosylate the human norepinephrine transporter reduces protein stability, surface trafficking, and transport activity but not ligand recognition.
1996,
Pubmed Melikian,
Human norepinephrine transporter. Biosynthetic studies using a site-directed polyclonal antibody.
1994,
Pubmed Nelson,
The family of Na+/Cl- neurotransmitter transporters.
1998,
Pubmed Pacholczyk,
Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.
1991,
Pubmed Plenge,
The activity of 25 paroxetine/femoxetine structure variants in various reactions, assumed to be important for the effect of antidepressants.
1987,
Pubmed Plenge,
Affinity modulation of [3H]imipramine, [3H]paroxetine and [3H]citalopram binding to the 5-HT transporter from brain and platelets.
1991,
Pubmed Qian,
Protein kinase C activation regulates human serotonin transporters in HEK-293 cells via altered cell surface expression.
1997,
Pubmed Qian,
Identification and characterization of antidepressant-sensitive serotonin transporter proteins using site-specific antibodies.
1995,
Pubmed Ramamoorthy,
Biosynthesis, N-glycosylation, and surface trafficking of biogenic amine transporter proteins.
1998,
Pubmed Rudnick,
The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release.
1992,
Pubmed Rudnick,
Bioenergetics of neurotransmitter transport.
1998,
Pubmed Rudnick,
Ion-coupled neurotransmitter transport: thermodynamic vs. kinetic determinations of stoichiometry.
1998,
Pubmed Rudnick,
From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters.
1993,
Pubmed Rudnick,
Sodium ion requirements for serotonin transport and imipramine binding.
1983,
Pubmed Sanger,
DNA sequencing with chain-terminating inhibitors.
1977,
Pubmed Sonders,
Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants.
1997,
Pubmed
,
Xenbase Stauffer,
Electrostatic potential of the acetylcholine binding sites in the nicotinic receptor probed by reactions of binding-site cysteines with charged methanethiosulfonates.
1994,
Pubmed Strader,
Allele-specific activation of genetically engineered receptors.
1991,
Pubmed Strader,
Structural basis of beta-adrenergic receptor function.
1989,
Pubmed Tatsumi,
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
1997,
Pubmed Wall,
Binding of the cocaine analog 2 beta-carbomethoxy-3 beta-(4-[125I]iodophenyl)tropane to serotonin and dopamine transporters: different ionic requirements for substrate and 2 beta-carbomethoxy-3 beta-(4-[125I]iodophenyl)tropane binding.
1993,
Pubmed White,
Cocaine and the serotonin saga.
1998,
Pubmed
