Primary Structure of the Human Platelet Serotonin Uptake Site: Identity with the Brain Serotonin Transporter


Address correspondence and reprint requests to Dr. K. P. Lesch at Department of Psychiatry, University of Würzburg, Füchs-leinstrasse 15, 8700 Würzburg, F.R.G.


Abstract: A cDNA encoding the human platelet serotonin (5-HT) uptake site was isolated and sequenced using the PCR. The cDNA represents a ˜3.1-kb mRNA transcript and contains an open reading frame encoding a hydrophobic polypeptide of 630 amino acids with 12 membrane-spanning segments, a calculated molecular mass of 70,320 Da, and an estimated isoelectrical point of 5.84. The human platelet 5-HT uptake site is identical with the human brain 5-HT transporter and ˜92% homologous to the rat protein. Hydropathicity analysis indicates 12 membrane-spanning segments with two putative glycosylation sites within the second extracellular loop. The human platelet 5-HT uptake site contains two intraplasmatic consensus phosphorylation sites for cyclic AMP-dependent protein kinase recognition located in the cytoplasmatic N-terminal region and three potential protein kinase C phosphorylation sites. The identity of the human platelet 5-HT uptake site and the brain 5-HT transporter indicates that both proteins are encoded by the same single-copy gene, which has been assigned to the human chromosome 17. Our findings are likely to facilitate molecular pharmacologic and genetic investigations of the 5-HT transporter in psychiatric disorders.