Figure 6.

A model for the desialylation-mediated GPIb-IX signaling and platelet clearance. In this model, exogenous neuraminidase removes sialic acids from O-glycans in GPIbα, thereby inducing unfolding of the mechanosensory (MSD), exposure of the Trigger sequence therein, GPIb-IX signaling into the platelet, surface expression of Neu1, and exposure of b-galactoses (b-Gal) on N-glycans of many glycoproteins, which are recognized by the Ashwell-Morell receptor and other receptors for clearance. Unfolding of the MSD also increases the accessibility of the ADAM17 shedding cleavage site in the MSD, facilitates shedding of GPIbα, which results in the exposure of the Trigger sequence.