 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, October 1, 1998, 18(19):7739-7749
Amino Acid Residues that Control pH Modulation of Transport-Associated Current in Mammalian Serotonin Transporters
Yongwei Cao, Ming Li, Sela Mager, and Henry A. Lester Division of Biology, California Institute of Technology, Pasadena, California 91125
The rat and human serotonin transporters (rSERT and hSERT, respectively) were expressed in Xenopus oocytes and studied using site-directed mutagenesis, electrophysiological recordings, and [3H]5-HT uptake measurements. rSERT, but not hSERT, displayed increased transport-associated current at low pH. Chimeras and point mutations showed that, of the 52 nonidentical residues, a single residue at position 490 (threonine in rSERT and lysine in hSERT) governs this difference. Furthermore, potentiation required the glutamate residue at position 493. Cysteine substitution and alkylation experiments showed that residue 493 is extracellular. Cysteine at 493 increased, whereas aspartate decreased, the net charge movement per transported 5-HT molecule. The mutations at this region did not significantly affect other aspects of SERT function, including agonist-independent leakage current, voltage-dependent transient current, and H+ current. This region may therefore be part of an external gate required for rSERT function. The data and analyses show that, in the absence of detailed structural information, a gate-lumen-gate scheme is useful for interpreting results from mutations that alter functional properties of neurotransmitter transporters.
Key words: 5-HT; Xenopus oocyte; protons; channels; electrophysiology; sodium
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197739-11$05.00/0
This article has been cited by other articles:
L. Celik, B. Schiott, and E. Tajkhorshid
Substrate Binding and Formation of an Occluded State in the Leucine Transporter
Biophys. J., March 1, 2008; 94(5): 1600 - 1612.
[Abstract] [Full Text] [PDF]
H. Iwamoto, R. D. Blakely, and L. J. De Felice
Na+, Cl-, and pH Dependence of the Human Choline Transporter (hCHT) in Xenopus Oocytes: The Proton Inactivation Hypothesis of hCHT in Synaptic Vesicles
J. Neurosci., September 27, 2006; 26(39): 9851 - 9859.
[Abstract] [Full Text] [PDF]
H. P. Koch and H. P. Larsson
Small-Scale Molecular Motions Accomplish Glutamate Uptake in Human Glutamate Transporters
J. Neurosci., February 16, 2005; 25(7): 1730 - 1736.
[Abstract] [Full Text] [PDF]
S. V. Adams and L. J. DeFelice
Ionic Currents in the Human Serotonin Transporter Reveal Inconsistencies in the Alternating Access Hypothesis
Biophys. J., September 1, 2003; 85(3): 1548 - 1559.
[Abstract] [Full Text] [PDF]
N. MacAulay, A.-K. Meinild, T. Zeuthen, and U. Gether
Residues in the Extracellular Loop 4 Are Critical for Maintaining the Conformational Equilibrium of the {gamma}-Aminobutyric Acid Transporter-1
J. Biol. Chem., August 1, 2003; 278(31): 28771 - 28777.
[Abstract] [Full Text] [PDF]
M. K. Hahn, D. Robertson, and R. D. Blakely
A Mutation in the Human Norepinephrine Transporter Gene (SLC6A2) Associated with Orthostatic Intolerance Disrupts Surface Expression of Mutant and Wild-Type Transporters
J. Neurosci., June 1, 2003; 23(11): 4470 - 4478.
[Abstract] [Full Text] [PDF]
T. E. Decoursey
Voltage-Gated Proton Channels and Other Proton Transfer Pathways
Physiol Rev, April 1, 2003; 83(2): 475 - 579.
[Abstract] [Full Text] [PDF]
S. V. Adams and L. J. DeFelice
Flux Coupling in the Human Serotonin Transporter
Biophys. J., December 1, 2002; 83(6): 3268 - 3282.
[Abstract] [Full Text] [PDF]
B. R. Stevens, D. H. Feldman, Z. Liu, and W. R. Harvey
Conserved tyrosine-147 plays a critical role in the ligand-gated current of the epithelial cation/amino acid transporter/channel CAATCH1
J. Exp. Biol., August 15, 2002; 205(16): 2545 - 2553.
[Abstract] [Full Text] [PDF]
M. Li and H. A. Lester
Early Fluorescence Signals Detect Transitions at Mammalian Serotonin Transporters
Biophys. J., July 1, 2002; 83(1): 206 - 218.
[Abstract] [Full Text] [PDF]
K. R. Aubrey, A. D. Mitrovic, and R. J. Vandenberg
Molecular Basis for Proton Regulation of Glycine Transport by Glycine Transporter Subtype 1b
Mol. Pharmacol., July 1, 2000; 58(1): 129 - 135.
[Abstract] [Full Text]
J. Ponce, B. Biton, J. Benavides, P. Avenet, and C. Aragon
Transmembrane Domain III Plays an Important Role in Ion Binding and Permeation in the Glycine Transporter GLYT2
J. Biol. Chem., April 28, 2000; 275(18): 13856 - 13862.
[Abstract] [Full Text] [PDF]
Y. Smicun, S. D. Campbell, M. A. Chen, H. Gu, and G. Rudnick
The Role of External Loop Regions in Serotonin Transport. LOOP SCANNING MUTAGENESIS OF THE SEROTONIN TRANSPORTER EXTERNAL DOMAIN
J. Biol. Chem., December 17, 1999; 274(51): 36058 - 36064.
[Abstract] [Full Text] [PDF]
E. L. Barker, K. R. Moore, F. Rakhshan, and R. D. Blakely
Transmembrane Domain I Contributes to the Permeation Pathway for Serotonin and Ions in the Serotonin Transporter
J. Neurosci., June 15, 1999; 19(12): 4705 - 4717.
[Abstract] [Full Text] [PDF]
Z. Qu, Z. Yang, N. Cui, G. Zhu, C. Liu, H. Xu, S. Chanchevalap, W. Shen, J. Wu, Y. Li, et al.
Gating of Inward Rectifier K+ Channels by Proton-mediated Interactions of N- and C-terminal Domains
J. Biol. Chem., October 6, 2000; 275(41): 31573 - 31580.
[Abstract] [Full Text] [PDF]
M. E. A. Reith, J. L. Berfield, L. C. Wang, J. V. Ferrer, and J. A. Javitch
The Uptake Inhibitors Cocaine and Benztropine Differentially Alter the Conformation of the Human Dopamine Transporter
J. Biol. Chem., July 27, 2001; 276(31): 29012 - 29018.
[Abstract] [Full Text] [PDF]
D. H. Feldman, W. R. Harvey, and B. R. Stevens
A Novel Electrogenic Amino Acid Transporter Is Activated by K+ or Na+, Is Alkaline pH-dependent, and Is Cl--independent
J. Biol. Chem., August 4, 2000; 275(32): 24518 - 24526.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|