title: The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function.
abstract: BACKGROUND
  Thiol isomerases are a family of endoplasmic reticulum enzymes which orchestrate redox-based modifications of protein disulphide bonds. Previous studies have identified important roles for the thiol isomerases PDI and ERp5 in the regulation of normal platelet function.
  
  
  OBJECTIVE
  Recently, we demonstrated the presence of a further five thiol isomerases at the platelet surface. In this report we aim to report the role of one of these enzymes - ERp57 in the regulation of platelet function.
  
  
  RESULTS
  Using enzyme activity function blocking antibodies, we demonstrate a role for ERp57 in platelet aggregation, dense granule secretion, fibrinogen binding, calcium mobilisation and thrombus formation under arterial conditions. In addition to the effects of ERp57 on isolated platelets, we observe the presence of ERp57 in the developing thrombus in vivo. Furthermore the inhibition of ERp57 function was found to reduce laser-injury induced arterial thrombus formation in a murine model of thrombosis.
  
  
  CONCLUSIONS
  These data suggest that ERp57 is important for normal platelet function and opens up the possibility that the regulation of platelet function by a range of cell surface thiol isomerases may represent a broad paradigm for the regulation of haemostasis and thrombosis.
authors.affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Berkshire, UK. lisa.holbrook@path.ox.ac.uk
authors.forename: L-M
authors.initials: LM
authors.lastname: Holbrook
authors.forename: P
authors.initials: P
authors.lastname: Sasikumar
authors.forename: R G
authors.initials: RG
authors.lastname: Stanley
authors.forename: A D
authors.initials: AD
authors.lastname: Simmonds
authors.forename: A B
authors.initials: AB
authors.lastname: Bicknell
authors.forename: J M
authors.initials: JM
authors.lastname: Gibbins
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010974:Platelet Aggregation; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism; D013927:Thrombosis / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D005340:Fibrinogen; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D002118:Calcium