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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents

ID: 194832.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release
Authors:Walther, Diego J.; Peter, Jens-Uwe; Winter, Sandra; Holtje, Markus; Paulmann, Nils; Grohmann, Maik; Vowinckel, Jakob; Alamo-Bethencourt, Victor; Wilhelm, Claudia S.; Ahnert-Hilger, Gudrun; Bader, Michael
Date of Publication (YYYY-MM-DD):2003-12-26
Title of Journal:Cell
Journal Abbrev.:Cell
Issue / Number:7
Start Page:851
End Page:862
Copyright:© 2003 Cell Press.
Review Status:not specified
Audience:Experts Only
Abstract / Description: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 -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 -granule exocytosis from platelets.
Comment of the Author/Creator:December 24, 2003
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:Max Planck Inst Mol Genet, D-14195 Berlin, Germany.; Humbolt Univ Berlin, Inst Anat, Charite, D-10117 Berlin, Germany.; Max Delbrueck Ctr Mol Med, D-13092 Berlin, Germany.
Identifiers:ISI:000187664700009 [ID No:1]
ISSN:0092-8674 [ID No:2]
DOI:10.1016/S0092-8674(03)01014-6 [ID No:3]
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