Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Display Documents



  history
ID: 191995.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Serotonylation of small GTPases is a signal transduction pathway that triggers platelet -granule release
Authors:Walther, Diego J.; Peter, Jens-Uwe; Winter, Sandra; Hötje, Markus; Paulmann, Nils; Grohmann, Maik; Vowinckel, Jakob; Alamo-Bethencourt, Victor; Wilhelm, Claudia S.; Ahnert-Hilger, Gudrun; Bader, Michael
Language:English
Date of Publication (YYYY-MM-DD):2003-12-26
Title of Journal:Cell
Journal Abbrev.:Cell
Volume:115
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.
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:Institute for Anatomy, Humboldt University Berlin, Charité, Philippstrasse 12, D-10117, Berlin, Germany
Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13092, Berlin-Buch, Germany
Identifiers:ISSN:0092-8674 [ID No:1]
DOI:10.1016/S0092-8674(03)01014-6 [ID No:2]
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.