Identification of novel Syk-independent functional roles of FcγRIIa in platelet outside-in signaling using transgenic mice expressing human FcγRIIa.

Platelet outside-in signaling regulates important morphological changes such as cell spreading and retraction. A role for FcγRIIa in outside-in signaling has been recently described. Using murine platelets expressing human transgenic FcγRIIa we expand the evidence for the role of human FcγRIIa in platelet outside-in signaling. Transgenic murine platelets spread more on fibrinogen when compared to WT platelets. Importantly, the role of FcγRIIa in clot retraction was independent of its association with Syk kinase as evidence by the kinetics of retraction with the Syk inhibitor OXSI-2. The enhanced platelet spreading in transgenic mice is reflected in increased Syk phosphorylation and activity as downstream targets PLCγ2 and c-Cbl Y774. Nonetheless, the WT counterparts exhibit phosphorylation of Syk and PLCγ2 suggesting that murine platelets have evolved an alternative FcγRIIa-independent outside-in signaling mechanism.