Open AccessMolecular and functional characterization of the Gulf toadfish serotonin transporter (SERT; SLC6A4)
Author(s) -
Molly H. B. Amador,
M. Danielle McDonald
Publication year - 2018
Publication title -
journal of experimental biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.367
H-Index - 185
eISSN - 1477-9145
pISSN - 0022-0949
DOI - 10.1242/jeb.170928
Subject(s) - serotonin transporter , serotonin , toadfish , neuroscience , serotonin plasma membrane transport proteins , biology , fishery , genetics , fish <actinopterygii> , receptor
The serotonin transporter (SERT) functions in the uptake of the neurotransmitter serotonin (5-HT) from the extracellular milieu and is the molecular target of the selective serotonin reuptake inhibitors (SSRIs), a common group of antidepressants. The current study comprehensively assesses the sequence, tissue distribution, transport kinetics, and physiological function of a teleost SERT. The 2,022-bp toadfish SERT sequence encodes a protein of 673 amino acids, which shows 83% similarity to zebrafish SERT and groups with SERT of other teleosts in phylogenetic analysis. SERT mRNA is ubiquitous in tissues and is expressed at high levels in the heart and, within the brain, in the cerebellum. SERT cRNA expressed in Xenopus laevis oocytes demonstrates a Km value of 2.08±0.45 µM, similar to previously reported Km values for zebrafish and human SERT. Acute systemic blockade of SERT by intraperitoneal administration of the SSRI fluoxetine (FLX) produces a dose-dependent increase in plasma 5-HT, indicating effective inhibition of 5-HT uptake from the circulation. As teleosts lack platelets, which are important 5-HT sequestration sites in mammals, the FLX-induced increase in plasma 5-HT suggests that toadfish tissues may normally be responsible for maintaining low 5-HT concentrations in the bloodstream.