The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells
Yp. Yuan et al., The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells, J BIOL CHEM, 274(51), 1999, pp. 36241-36251
Platelet adhesion to sites of vascular injury is initiated by the binding o
f the platelet glycoprotein (GP) Ib-V-M complex to matrix-bound von Willebr
and factor (vWf). This receptor-ligand interaction is characterized by a ra
pid on-off rate that enables efficient platelet tethering and rolling under
conditions of rapid blood flow. We demonstrate here that platelets adherin
g to immobilized vWf under flow conditions undergo rapid morphological conv
ersion from flat discs to spiny spheres during surface translocation. Studi
es of Glanzmann thrombasthenic platelets (lacking integrin alpha(IIb)beta(3
)) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/I
X) confirmed that vWf binding to GPIb/IX was sufficient to induce actin pol
ymerization and cytoskeletal reorganization independent of integrin alpha(I
Ib)beta(3). vWf-induced cytoskeletal reorganization occurred independently
of several well characterized signaling processes linked to platelet activa
tion, including calcium influx, prostaglandin metabolism, protein tyrosine
phosphorylation, activation of protein kinase C or phosphatidylinositol 3-k
inase but was critically dependent on the mobilization of intracellular cal
cium. Studies of Oregon Green 488 1,2-bis(o-amino-5-fluorophenoxy)ethane-N,
N,N',N-tetraacetic acid tetraacetoxymethyl ester-loaded platelets and CHO-I
b/IX cells demonstrated that these cells mobilize intracellular calcium in
a shear-dependent manner during surface translocation on vWf. Taken togethe
r, these studies suggest that the vWf-GPIb interaction stimulates actin pol
ymerization and cytoskeletal reorganization in rolling platelets via a shea
r-sensitive signaling pathway linked to intracellular calcium mobilization.