Binding of galectin-1 to alphaIIbbeta3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis

ROMANIUK, MA; CROCI DO; LAPPONI, MJ; TRIBULATTI MV; NEGROTTO, S; POIRIER, F; CAMPETELLA, O; RABINOVICH, GA; SCHATTNER, M

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2012 vol. 26 p. 2788 - 2798

0892-6638

Understanding noncanonical mechanismsof platelet activation represents an important challengefor the identification of novel therapeutic targets inbleeding disorders, thrombosis, and cancer. We previouslyreported that galectin-1 (Gal-1), a beta-galactoside-bindingprotein, triggers platelet activation in vitro. Herewe investigated the molecular mechanisms underlying thisfunction and the physiological relevance of endogenousGal-1 in hemostasis. Mass spectrometry analysis, as well asstudies using blocking antibodies against the anti-IIbsubunit of alphaIIbbeta3 integrin or platelets from patients withGlanzmann?s thrombasthenia syndrome (alphaIIbbeta3 deficiency),identified this integrin as a functional Gal-1receptor in platelets. Binding of Gal-1 to platelets triggeredthe phosphorylation of beta3-integrin, Syk, MAPKs,PI3K, PLCgamma2, thromboxane (TXA2) release, and Ca2+mobilization. Not only soluble but also immobilized Gal-1promoted platelet activation. Gal-1-deficient (Lgals1-/-)mice showed increased bleeding time (P