Serotonylation of Small GTPases Is a Signal Transduction Pathway that Triggers Platelet α-Granule Release

276Citations
Citations of this article
160Readers
Mendeley users who have this article in their library.

Abstract

Serotonin is a neurotransmitter in the central nervous system. In the periphery, serotonin functions as a ubiquitous hormone involved in vasoconstriction and platelet function. Serotonin is synthesized independently in peripheral tissues and neurons by two different rate-limiting tryptophan hydroxylase (TPH) isoenzymes. Here, we show that mice selectively deficient in peripheral TPH and serotonin exhibit impaired hemostasis, resulting in a reduced risk of thrombosis and thromboembolism, although the ultrastructure of the platelets is not affected. While the aggregation of serotonin-deficient platelets in vitro is apparently normal, their adhesion in vivo is reduced due to a blunted secretion of adhesive α-granular proteins. In elucidating the mechanism further, we demonstrate that serotonin is transamidated to small GTPases by transglutaminases during activation and aggregation of platelets, rendering these GTPases constitutively active. Our data provides evidence for a receptor-independent signaling mechanism, termed herein as "serotonylation, " which leads to α-granule exocytosis from platelets.

Cite

CITATION STYLE

APA

Walther, D. J., Peter, J. U., Winter, S., Höltje, M., Paulmann, N., Grohmann, M., … Bader, M. (2003). Serotonylation of Small GTPases Is a Signal Transduction Pathway that Triggers Platelet α-Granule Release. Cell, 115(7), 851–862. https://doi.org/10.1016/S0092-8674(03)01014-6

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free