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.
Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound von Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate here that platelets adhering to immobilized vWf under flow conditions undergo rapid morphological conversion from flat discs to spiny spheres during surface translocation. Studies of Glanzmann thrombasthenic platelets (lacking integrin alpha(IIb)beta(3)) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/IX) confirmed that vWf binding to GPIb/IX was sufficient to induce actin polymerization and cytoskeletal reorganization independent of integrin alpha(IIb)beta(3). vWf-induced cytoskeletal reorganization occurred independently of several well characterized signaling processes linked to platelet activation, including calcium influx, prostaglandin metabolism, protein tyrosine phosphorylation, activation of protein kinase C or phosphatidylinositol 3-kinase but was critically dependent on the mobilization of intracellular calcium. 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-Ib/IX cells demonstrated that these cells mobilize intracellular calcium in a shear-dependent manner during surface translocation on vWf. Taken together, these studies suggest that the vWf-GPIb interaction stimulates actin polymerization and cytoskeletal reorganization in rolling platelets via a shear-sensitive signaling pathway linked to intracellular calcium mobilization.
Yuan
Y
Y
Australian Centre for Blood Diseases, Department of Medicine, Monash Medical School, Victoria, Australia.
Kulkarni
S
S
Ulsemer
P
P
Cranmer
S L
SL
Yap
C L
CL
Nesbitt
W S
WS
Harper
I
I
Mistry
N
N
Dopheide
S M
SM
Hughan
S C
SC
Williamson
D
D
de la Salle
C
C
Salem
H H
HH
Lanza
F
F
Jackson
S P
SP
D000199:Actins / Q000737:chemistry / Q000502:physiology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology / Q000648:ultrastructure; D016466:CHO Cells; D006224:Cricetinae; D003599:Cytoskeleton / Q000502:physiology*; D019281:Dimerization; D010974:Platelet Aggregation / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000502:physiology*; D014162:Transfection; D014841:von Willebrand Factor / Q000737:chemistry / Q000502:physiology*
D000199:Actins; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor