title: Membrane lipid rafts coordinate estrogen-dependent signaling in human platelets.
abstract: The impact of estrogens on the viability of cardiovascular system and their ability to regulate platelet function is still an open and debated question. We have previously shown that estrogen is able to significantly potentiate the aggregation induced by low doses of thrombin and to initiate a rapid and reversible signaling pathway mediated by ERbeta-directed activation of the tyrosine kinases Src and Pyk2 at the level of the plasma membrane. Lipid rafts are critical, cholesterol-enriched membrane domains, which play a major role in blood platelet activation processes. In this work, we investigated the role of lipid rafts in 17beta-estradiol signaling in human platelets. We observed that membrane rafts were essential for both 17beta-estradiol-dependent potentiation of platelet aggregation induced by subthreshold concentrations of thrombin and 17beta-estradiol-induced phosphorylation of Src. 17beta-estradiol caused the reversible translocation of ERbeta to the raft fractions and promoted the rapid and transient recruitment to, and activation within the membrane raft domains of the tyrosine kinases Src and Pyk2. The raft integrity was essential with this respect, as these effects of 17beta-estradiol were completely inhibited by cholesterol depletion. This paper provides evidence for the first time that membrane lipid rafts coordinate estrogen signaling in human platelets.
authors.affiliation: Department of Medical Sciences, University "A. Avogadro", Via Solaroli 17, 28100-Novara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Reineri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoni
authors.forename: Elena
authors.initials: E
authors.lastname: Sanna
authors.forename: Samantha
authors.initials: S
authors.lastname: Baldassarri
authors.forename: Chiara
authors.initials: C
authors.lastname: Sarasso
authors.forename: Manuela
authors.initials: M
authors.lastname: Zanfa
authors.forename: Ilaria
authors.initials: I
authors.lastname: Canobbio
authors.forename: Mauro
authors.initials: M
authors.lastname: Torti
authors.forename: Fabiola
authors.initials: F
authors.lastname: Sinigaglia
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002499:Centrifugation, Density Gradient; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000378:metabolism; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects* / Q000201:enzymology; D010974:Platelet Aggregation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D047629:Estrogen Receptor beta; D004958:Estradiol; D019061:src-Family Kinases; D013917:Thrombin