Cytoskeletal regulation of the platelet glycoprotein Ib/V/IX-von willebrand factor interaction
| Autor: | N, Mistry, S L, Cranmer, Y, Yuan, P, Mangin, S M, Dopheide, I, Harper, S, Giuliano, D E, Dunstan, F, Lanza, H H, Salem, S P, Jackson |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Blood Platelets
Cytochalasin D Platelet Aggregation CHO Cells Platelet Glycoprotein GPIIb-IIIa Complex Transfection Peptides Cyclic Cricetinae Depsipeptides von Willebrand Factor Animals Humans Alprostadil Cytoskeleton Antibodies Monoclonal Bridged Bicyclo Compounds Heterocyclic Actins Adenosine Diphosphate Actin Cytoskeleton Thiazoles Platelet Glycoprotein GPIb-IX Complex Mutagenesis Site-Directed Thiazolidines Stress Mechanical Platelet Aggregation Inhibitors Thrombasthenia |
| Zdroj: | Blood. 96(10) |
| ISSN: | 0006-4971 |
| Popis: | Shear-induced binding of von Willebrand factor (vWf) to the platelet glycoprotein (GP) Ib/V/IX complex plays a key role in initiating platelet adhesion and aggregation at sites of vascular injury. This study demonstrated that pretreating human platelets with inhibitors of actin polymerization, cytochalasin D or latrunculin B, dramatically enhances platelet aggregation induced by vWf. The effects of these inhibitors were specific to the vWf-GPIbalpha interaction because they enhanced vWf-induced aggregation of Glanzmann thrombasthenic platelets and Chinese hamster ovary (CHO) cells transfected with GPIb/V/IX. Moreover, cytochalasin D enhanced the extent of platelet aggregation induced by high shear stress (5000 s(-1)) and also lowered the shear threshold required to induce aggregation from 3000 s(-1) to as low as 500 s(-1). Studies of CHO cells expressing GPIbalpha cytoplasmic tail truncation mutants that failed to bind actin-binding protein-280 (deletion of residues 569-610 or 535-568) demonstrated that the linkage between GPIb and actin-binding protein-280 was not required for vWf-induced actin polymerization, but was critical for the enhancing effects of cytochalasin D on vWf-induced cell aggregation. Taken together, these studies suggest a fundamentally important role for the cytoskeleton in regulating the adhesive function of GPIb/V/IX. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|