Evidence for two mechanisms of ligand-receptor movement on surface-activated platelets.
The movement of platelet membrane glycoproteins was studied by correlative light and electron microscopy. Two distinct classes of movement were seen. In the first type, binding of colloidal gold-labeled ligand or antibody to the fibrinogen receptor (GPIIb/IIIa) triggered a long-range centripetal movement of the receptor-ligand complexes, in the plane of the membrane, on the surfaces of fully spread platelets. This movement was dependent on the presence of the intact cytoplasmic actin cytoskeleton, as evidenced by its inhibition by treatment of the platelets with cytochalasins D and E to disrupt actin filaments. A second surface receptor, the platelet von Willebrand's factor receptor (GPIb), did not undergo this long range, actin-dependent movement in response to antibody binding. However, in a second class of movement, both GPIb and GPIIb/IIIa were translocated on the platelet membrane. Both receptors, GPIb and GPIIb/IIIa, in response to binding of gold-labeled antibody or ligand, accumulated in the channels of the open canalicular system when these were present, and between platelets, under the platelet margins at the sites of platelet-platelet contact. This type of movement occurred only over a much shorter distance than the centripetal movement seen with ligand-bound GPIIb/IIIa and was not affected by the disruption of filamentous actin by the cytochalasins. These results suggest that there are two active mechanisms driving ligand-receptor movement on surface-activated platelets, and that one receptor type may be driven by either mechanism. However, each mechanism predominates at a different stage in the sequence of platelet activation, adherence, and spreading, consistent with differences in function related to receptor-ligand complex formation at the different stages.
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706.
O E
OE
Olorundare
S R
SR
Simmons
R M
RM
Albrecht
D000199:Actins / Q000187:drug effects; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D015638:Cytochalasin D / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D006801:Humans; D008024:Ligands; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011940:Receptor Aggregation / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism
D000199:Actins; D003572:Cytochalasins; D008024:Ligands; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor; D015638:Cytochalasin D; C007215:cytochalasin E