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

• Ionic interactions in the Drosophila serotonin transporter identify it as a serotonin channel [2].
• To examine SERT's response to high 5HT concentrations, we expressed Drosophila SERT (dSERT) in Xenopus oocytes and found that transport continued to increase with concentration up to 0.3 mM 5HT [2].
• A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization [3].
• Sequence analysis indicates 12 putative transmembrane domains and strong homologies (approximately 50%) among dSERT1 and mammalian 5HT, norepinephrine, and dopamine transporters [3].
• Cloning, expression, and localization of a chloride-facilitated, cocaine-sensitive serotonin transporter from Drosophila melanogaster [1].

Biological context of SerT

• Loss of robo2 or robo3 causes a loss of SerT expression in about half of neurons, and resembles the phenotype seen in mutants for the transcription factor eagle (eg) [4].
• The dSERT gene was mapped to position 60C on chromosome 2 [1].
• 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 [5].
• A 1.1-kb spliced form of SERT was also identified by reverse transcription polymerase chain reaction analysis [6].
• In summary, a novel gene product expressed primarily by Sertoli cells, SERT, was identified with a potential RNA binding protein motif similar to sex lethal that appears to have a role in maintaining hormone (e.g. FSH) actions in Sertoli cells [6].

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

• The expression pattern of SERT was examined with reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis [6].

References