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

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

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Genre: Zeitschriftenartikel
Alternativer Titel : Cell

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Walther, Diego J.1, Autor           
Peter, Jens-Uwe1, Autor           
Winter, Sandra, Autor
Holtje, Markus, Autor
Paulmann, Nils1, Autor           
Grohmann, Maik1, Autor           
Vowinckel, Jakob1, Autor           
Alamo-Bethencourt, Victor1, Autor           
Wilhelm, Claudia S., Autor
Ahnert-Hilger, Gudrun, Autor
Bader, Michael, Autor
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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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2003-12-26
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: eDoc: 194832
ISI: 000187664700009
DOI: 10.1016/S0092-8674(03)01014-6
 Art des Abschluß: -

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Titel: Cell
  Alternativer Titel : Cell
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 115 (7) Artikelnummer: - Start- / Endseite: 851 - 862 Identifikator: ISSN: 0092-8674