Molecular Mechanisms of SERT in Platelets: Regulation of Plasma Serotonin Levels

Abstract

Long before it received fame as a neurotransmitter, 5-hydroxytryptamine was recognized as a vasoconstrictor in serum and therefore termed “serotonin.” Elevated serotonin levels in the plasma have been linked to hypertension and various cardiovascular diseases. The serotonin transporter (SERT) located in the platelet plasma membrane is the fundamental regulator of plasma serotonin concentration. Intriguingly, the expression of SERT in the platelet membrane is regulated by plasma levels of serotonin, and recent research reveals that the trafficking of SERT between the plasma membrane and platelet cytoplasm occurs in a highly dynamic context that includes phosphate signaling and small G proteins, protein serotonylation, and essential components of platelet activation. The interplay of plasma serotonin and platelet activation may have particular implications for the treatment of cardiovascular disease.