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Titolo:
Transmembrane domain I contributes to the permeation pathway for serotoninand ions in the serotonin transporter
Autore:
Barker, EL; Moore, KR; Rakhshan, F; Blakely, RD;
Indirizzi:
Vanderbilt Univ, Ctr Mol Neurosci, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 12, volume: 19, anno: 1999,
pagine: 4705 - 4717
SICI:
0270-6474(19990615)19:12<4705:TDICTT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN NOREPINEPHRINE TRANSPORTER; AMINOBUTYRIC-ACID TRANSPORTER; HUMAN DOPAMINE TRANSPORTER; RAT-BRAIN; NEUROTRANSMITTER TRANSPORTERS; EXPRESSION CLONING; COCAINE BINDING; RNA-POLYMERASE; HEK-293 CELLS; AMINO-ACID;
Keywords:
serotonin; monoamine; transporter; biological transport; carrier proteins; molecular structure; permeation channel; selectivity filter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Blakely, RD Vanderbilt7232v, Ctr Mol Neurosci, Sch Med, MRBII Room 419, Nashville, TN 3 Vanderbilt Univ MRBII Room 419 Nashville TN USA 37232 le, TN 3
Citazione:
E.L. Barker et al., "Transmembrane domain I contributes to the permeation pathway for serotoninand ions in the serotonin transporter", J NEUROSC, 19(12), 1999, pp. 4705-4717

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 K-m value. D98E, which extends the acidic side chainby 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 abilityof 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.

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Documento generato il 11/07/20 alle ore 18:59:12