cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 3; pp. 1188 - 1192
• Main Authors: Corey, J.L, Quick, M.W, Davidson, N, Lester, H.A, Guastella, J
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.02.1994; National Acad Sciences; National Academy of Sciences
• Subjects: active transport; Amino Acid Sequence; amino acid sequences; Amino acids; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Binding and carrier proteins; binding proteins; Biological and medical sciences; Biology; Carrier Proteins - drug effects; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cloning, Molecular; Cocaine; Cocaine - pharmacology; complementary DNA; DNA Primers - genetics; DNA, Complementary - genetics; Drosophila; Drosophila - genetics; Drosophila - metabolism; Drosophila melanogaster; Drosophila Proteins; Electric current; Electrophysiology; Female; Fundamental and applied biological sciences. Psychology; genbank/u02296; Gene Expression; Genes, Insect; Humans; Insects; Membrane Glycoproteins - drug effects; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; membrane potential; Membrane Transport Proteins; Messenger RNA; Molecular Sequence Data; Nerve Tissue Proteins; Neurology; Neurons; Neurotransmitters; Norepinephrine; nucleotide sequences; Oocytes; Oocytes - metabolism; Pharmacology; plasma membrane; Proteins; Rats; Sequence Homology, Amino Acid; serotonin; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins; Xenopus; Purification; Serotonin; Insecta; Interspecific comparison; Drosophila; Sequence alignment; Electrophysiology; Biological activity; Drosophilidae; Arthropoda; Neurotransmitter; Invertebrata; Diptera; Carrier protein; Aminoacid sequence; Structural analysis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.3.1188

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.