title: Rho associated coiled-coil kinase-1 regulates collagen-induced phosphatidylserine exposure in platelets.
abstract: BACKGROUND
  The transbilayer movement of phosphatidylserine mediates the platelet procoagulant activity during collagen stimulation. The Rho-associated coiled-coil kinase (ROCK) inhibitor Y-27632 inhibits senescence induced but not activation induced phosphatidylserine exposure. To investigate further the specific mechanisms, we now utilized mice with genetic deletion of the ROCK1 isoform.
  
  
  RESULTS
  ROCK1-deficient mouse platelets expose significantly more phosphatidylserine and generate more thrombin upon activation with collagen compared to wild-type platelets. There were no significant defects in platelet shape change, aggregation, or calcium response compared to wild-type platelets. Collagen-stimulated ROCK1-deficient platelets also displayed decreased phosphorylation levels of Lim Kinase-1 and cofilin-1. However, there was no reduction in phosphorylation levels of myosin phosphatase subunit-1 (MYPT1) or myosin light chain (MLC). In an in vivo light/dye-induced endothelial injury/thrombosis model, ROCK1-deficient mice presented a shorter occlusion time in cremasteric venules when compared to wild-type littermates (3.16 ± 1.33 min versus 6.6 ± 2.6 min; p = 0.01).
  
  
  CONCLUSIONS
  These studies define ROCK1 as a new regulator for collagen-induced phosphatidylserine exposure in platelets with functional consequences on thrombosis. This effect was downstream of calcium signaling and was mediated by Lim Kinase-1 / cofilin-1-induced cytoskeletal changes.
authors.affiliation: Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Dasgupta
authors.affiliation: Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Anhquyen
authors.initials: A
authors.lastname: Le
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Haudek
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Entman
authors.affiliation: Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Rolando E
authors.initials: RE
authors.lastname: Rumbaut
authors.affiliation: Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Perumal
authors.initials: P
authors.lastname: Thiagarajan
mesh_terms: D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051338:Cofilin 1 / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010718:Phosphatidylserines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D013917:Thrombin / Q000096:biosynthesis; D013927:Thrombosis / Q000235:genetics; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000577:Amides; D051338:Cofilin 1; D010718:Phosphatidylserines; D011725:Pyridines; C108830:Y 27632; D003094:Collagen; D054461:Lim Kinases; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D013917:Thrombin