A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization.
A cocaine-sensitive, high-affinity Drosophila serotonin (5-hydroxytryptamine; 5HT) transporter cDNA, denoted dSERT1, was isolated and characterized in oocytes. dSERT1 shows little transport of other monoamines and is Na+ and Cl- dependent. Sequence analysis indicates 12 putative transmembrane domains and strong homologies (approximately 50%) among dSERT1 and mammalian 5HT, norepinephrine, and dopamine transporters. Interestingly, the pharmacological properties of dSERT1, including sensitivity to antidepressants, are more similar to those of mammalian catecholamine transporters than to mammalian 5HT transporters. Two-electrode voltage-clamp analysis demonstrated 5HT-induced, voltage-dependent currents. Cloning and characterization of dSERT1 adds significantly to our knowledge of the diversity of 5HT transporters with regard to primary sequence, pharmacological profile, and permeation properties.
Corey
J L
JL
Division of Biology 156-29, California Institute of Technology, Pasadena 91125.
Quick
M W
MW
Davidson
N
N
Lester
H A
HA
Guastella
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D003042:Cocaine / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression; D017344:Genes, Insect; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D014981:Xenopus
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; C493233:SerT protein, Drosophila; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D003042:Cocaine