Platelet Activation and “Crossover Appeal”: Rab and Rho Families United by Common Links to Serotonin

Abstract

Tryptophan hydroxylase 1 (Tph1) is essential for the production of serotonin. Tph1^−/− mice have increased risk of thromboembolism, although there appears to be no observable change to the ultrastructure of the platelets in the knockout mice. The platelets are deficient in their ability to adhere to wounded surfaces and this arises from a decrement in secreted adhesive granular proteins. Surprisingly, the defective function of the platelets can be traced back to an impairment in the transamidation of Rab4 and RhoA by serotonin. During the normal process of platelet activation and granular protein secretion, these GTPases are activated; however, in the knockout mice, lack of serotonin translates into lack of platelet activation and adhesion, leading to increased likelihood of thrombosis.