Titre
Production of phosphatidylinositol 3,4,5-trisphosphate and phosphatidic acid in platelet rafts: evidence for a critical role of cholesterol-enriched domains in human platelet activation.
Type
article
Institution
Externe
Périodique
Auteur(s)
Bodin, S.
Auteure/Auteur
Giuriato, S.
Auteure/Auteur
Ragab, J.
Auteure/Auteur
Humbel, B.M.
Auteure/Auteur
Viala, C.
Auteure/Auteur
Vieu, C.
Auteure/Auteur
Chap, H.
Auteure/Auteur
Payrastre, B.
Auteure/Auteur
Liens vers les personnes
ISSN
0006-2960
Statut éditorial
Publié
Date de publication
2001
Volume
40
Numéro
50
Première page
15290
Dernière page/numéro d’article
15299
Langue
anglais
Résumé
Glycosphingolipid- and cholesterol-enriched membrane microdomains, called rafts, can be isolated from several mammalian cells, including platelets. These microdomains appear to play a critical role in signal transduction in several hematopoietic cells, but their function in blood platelets remains unknown. Herein, we first characterized the lipid composition, including the fatty acid composition of phospholipids, of human platelet rafts. Then their role in platelet activation process was investigated. Interestingly, thrombin stimulation led to morphological changes of rafts correlating with the production of lipid second messengers in these microdomains. Indeed, we could demonstrate for the first time that a large part of the stimulation-dependent production of phosphatidic acid and phosphoinositide 3-kinase products was concentrated in rafts. Moreover, cholesterol depletion with methyl-beta-cyclodextrin disrupted platelet rafts, dramatically decreased the agonist-dependent production of these lipid signaling molecules, and impaired platelet secretion and aggregation. Cholesterol repletion restored the physiological platelet responses. Altogether our data indicate that rafts are highly dynamic platelet membrane structures involved in critical signaling mechanisms linked to the production of lipid second messengers. The demonstration of phosphatidylinositol 3,4,5-trisphosphate production in rafts may have general implications for the understanding of the role of this key second messenger found ubiquitously in higher eucaryotic cells.
PID Serval
serval:BIB_CD3210B98DAE
PMID
Date de création
2012-10-18T13:12:34.939Z
Date de création dans IRIS
2025-05-20T21:55:10Z