title: Extracellular Thiol Isomerases and Their Role in Thrombus Formation.
abstract: CONCLUSIONS
  The mammalian endoplasmic reticulum (ER) houses a large family of twenty thioredoxin-like proteins of which protein disulfide isomerase (PDI) is the archetypal member. Although the PDI family is best known for its role in oxidative protein folding of secretory proteins in the ER, these thioredoxin-like proteins fulfill ever-expanding roles, both within the secretory pathway and beyond.
  
  
  BACKGROUND
  Secreted PDI family proteins have now been shown to serve a critical role in platelet thrombus formation and fibrin generation. Utilizing intravital microscopy to visualize thrombus formation in mice, we have demonstrated the presence of extracellular PDI antigen during thrombus formation following injury of the vascular wall. Inhibition of PDI abrogates thrombus formation in vivo (16, 26, 46, 55). These observations have been extended to other PDI family members, including ERp57 (39, 116, 118, 123) and ERp5 (77). The vascular thiol isomerases are those PDI family members secreted from platelets and/or endothelium (40): PDI, ERp57, ERp5, ERp72, ERp44, ERp29, and TMX3. We focus here on PDI (16, 46, 55), ERp57 (39, 116, 118, 123), and ERp5 (77), which have been implicated in thrombus formation in vivo.
  
  
  RESULTS
  It would appear that a system of thiol isomerase redox catalysts has been hijacked from the ER to regulate thrombus formation in the vasculature.
  
  
  CONCLUSIONS
  How this redox system is trafficked to and regulated at the cell surface, the identity of extracellular substrates, why so many thiol isomerases are required, and which thiol isomerase functions are necessary are critical unanswered questions in understanding the role of thiol isomerases in thrombus formation.
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Sol
authors.initials: S
authors.lastname: Schulman
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Pavan
authors.initials: P
authors.lastname: Bendapudi
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Anish
authors.initials: A
authors.lastname: Sharda
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Vivien
authors.initials: V
authors.lastname: Chen
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Lola
authors.initials: L
authors.lastname: Bellido-Martin
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Reema
authors.initials: R
authors.lastname: Jasuja
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Furie
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Flaumenhaft
authors.affiliation: Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts.
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
mesh_terms: D000818:Animals; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D039661:Integrin beta3; D019704:Protein Disulfide-Isomerases