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Gene Review

SerT  -  Serotonin transporter

Drosophila melanogaster

Synonyms: 5HT transporter, 5HTT, CG4545, Cocaine-sensitive serotonin transporter, DmSERT, ...
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Disease relevance of SerT

  • In situ hybridization reveals the selective expression of dSERT mRNA to specific cell bodies in the ventral ganglion of the embryonic and larval Drosophila nervous system with a distribution pattern virtually identical to that of 5HT-containing neurons [1].

High impact information on SerT


Biological context of SerT


Anatomical context of SerT

  • 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 [3].
  • Upon transient expression in HeLa cells, dSERT exhibited saturable, high-affinity, and sodium-dependent [3H]5HT uptake with estimated Km and Vmax values of approximately 500 nM and 5.2 x 10(-18) mol per cell per min, respectively [1].
  • Treatment of cultured Sertoli cells with follicle stimulating hormone (FSH) significantly increased the expression of SERT mRNA levels [6].
  • SERT expression was found to be specific to the testis and absent in other tissues examined [6].
  • Molecular cloning of a serotonin transporter from the central nervous system of the insect Manduca sexta enabled us to define domains that affect antagonist action, particularly cocaine [7].

Associations of SerT with chemical compounds

  • Both cocaine and RTI-55 inhibited 5HT uptake by dSERT with estimated inhibition constants of approximately 500 nM, while high concentrations (> 10 microM) of dopamine, norepinephrine, octopamine, tyramine, and histamine failed to inhibit transport [1].
  • By using human and Drosophila SERT chimeras, major determinants of potencies of two transporter antagonists, mazindol and citalopram, were tracked to the amino-terminal domains encompassing transmembrane domains I and II [5].
  • Despite the critical role of SERT in 5-HT inactivation and psychostimulant response, many aspects of the transporter's recognition of ligands are poorly defined [8].
  • Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition [8].
  • Tryptamine derivatives with substitutions at the 4 and 7 positions on the phenyl ring, the indole nitrogen, and the beta position show up to 40-fold potency differences for inhibiting [(3)H]5-HT transport in cells transfected with either human or Drosophila melanogaster SERT cDNAs [8].

Analytical, diagnostic and therapeutic context of SerT


  1. Cloning, expression, and localization of a chloride-facilitated, cocaine-sensitive serotonin transporter from Drosophila melanogaster. Demchyshyn, L.L., Pristupa, Z.B., Sugamori, K.S., Barker, E.L., Blakely, R.D., Wolfgang, W.J., Forte, M.A., Niznik, H.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Ionic interactions in the Drosophila serotonin transporter identify it as a serotonin channel. Petersen, C.I., DeFelice, L.J. Nat. Neurosci. (1999) [Pubmed]
  3. A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization. Corey, J.L., Quick, M.W., Davidson, N., Lester, H.A., Guastella, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation. Couch, J.A., Chen, J., Rieff, H.I., Uri, E.M., Condron, B.G. Development (2004) [Pubmed]
  5. High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol. Barker, E.L., Perlman, M.A., Adkins, E.M., Houlihan, W.J., Pristupa, Z.B., Niznik, H.B., Blakely, R.D. J. Biol. Chem. (1998) [Pubmed]
  6. Identification of a novel Sertoli cell gene product SERT that influences follicle stimulating hormone actions. Chaudhary, J., Sadler-Riggleman, I., Skinner, M.K. Gene (2004) [Pubmed]
  7. A cocaine insensitive chimeric insect serotonin transporter reveals domains critical for cocaine interaction. Sandhu, S.K., Ross, L.S., Gill, S.S. Eur. J. Biochem. (2002) [Pubmed]
  8. Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition. Adkins, E.M., Barker, E.L., Blakely, R.D. Mol. Pharmacol. (2001) [Pubmed]
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