alpha IIb beta 3 redistribution triggered by receptor cross-linking

Fibrinogen binding to alpha II beta 3 on adherent, spread platelets triggers active, cytoskeletally-directed redistribution of fibrinogen/alpha aIIb beta 3 complexes on the platelet surface. Gold-conjugated fibrinogen, unlabeled, soluble fibrinogen, and individual fibrinogen molecules have been demonstrated to trigger receptor redistribution. Here we examine the respective roles of receptor cross-linking and ligand occupancy of receptors in initiating this movement. Monovalent, alpha IIb beta 3-binding fibrinogen fragments RGDS and HHLGGAKQAGDV did not trigger receptor redistribution, suggesting that ligand binding to a single receptor is an insufficient stimulus. Binding of monoclonal antibodies 10E5, AP2, and AP3 to the receptor did not trigger receptor movement. However, cross-linking these receptor-bound monoclonal antibodies by polyclonal anti-mouse IgG or by conjugation of the anti-receptor antibody to large colloidal gold particles triggered receptor redistribution identical in rate, pattern, and final distribution to that previously seen with fibrinogen binding. We conclude that receptor crosslinking provides the signal for initiation of fibrinogen/alpha IIb beta 3 complex redistribution on platelet surfaces.