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  Serotonylation of small GTPases is a signal transduction pathway that triggers platelet -granule release

Walther, D. J., Peter, J.-U., Winter, S., Hötje, M., Paulmann, N., Grohmann, M., et al. (2003). Serotonylation of small GTPases is a signal transduction pathway that triggers platelet -granule release. Cell, 115(7), 851-862. doi:10.1016/S0092-8674(03)01014-6.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8946-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8947-9
Genre: Journal Article
Alternative Title : Cell

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 Creators:
Walther, Diego J.1, Author              
Peter, Jens-Uwe1, Author              
Winter, Sandra, Author
Hötje, Markus, Author
Paulmann, Nils1, Author              
Grohmann, Maik1, Author              
Vowinckel, Jakob1, Author              
Alamo-Bethencourt, Victor1, Author              
Wilhelm, Claudia S., Author
Ahnert-Hilger, Gudrun, Author
Bader, Michael, Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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 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 -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.

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Language(s): eng - English
 Dates: 2003-12-26
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 191995
DOI: 10.1016/S0092-8674(03)01014-6
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Title: Cell
  Alternative Title : Cell
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 115 (7) Sequence Number: - Start / End Page: 851 - 862 Identifier: ISSN: 0092-8674