BINDING OF GALECTIN-1 TO ALPHAIIB BETA3 INTEGRIN TRIGGERS OUTSIDE-IN SIGNALS, STIMULATES PLATELET ACTIVATION AND CONTROLS PRIMARY HEMOSTASIS

ROMANIUK MA; CROCI D0; LAPPONI MJ; TRIBULATTI MV; NEGROTTO S; POIRIER F; CAMPETELLA O; RABINOVICH GA*; SCHATTNER M* (*GAR Y MS COMPARTEN ÚLTIMA AUTORÍA)

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

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

0892-6638

Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a β-galactoside-binding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-αIIb subunit ofαIIbβ3 integrin or platelets from patients with Glanzmann´s thrombasthenia syndrome (αIIbβ3 deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of β3-integrin, Syk, MAPKs, PI3K, PLCγ2, thromboxane (TXA2) release, and Ca2+ mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1−/−) mice showed increased bleeding time (P