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 (≈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.
© 1993 National Academy of Sciences. Contributed by Norman Davidson, October 1, 1993. We thank Bruce Hamilton for providing us with the Drosophila head library, Jonathan Bradley for Drosophila embryo RNA, Susan R. Halsell for providing Drosophila for RNA preparation, and E. Davidson for use of a DNA sequenator. This research was supported by grants from the U.S. Public Health Service (Grant NS-11756 and National Research Service Award Fellowships to J.L.C., M.W.Q., and J.G.).
Published - PNAS-1994-Corey-1188-92.pdf