Platelets release novel thiol isomerase enzymes which are recruited to the cell surface following activation.
The thiol isomerase enzymes protein disulphide isomerase (PDI) and endoplasmic reticulum protein 5 (ERp5) are released by resting and activated platelets. These re-associate with the cell surface where they modulate a range of platelet responses including adhesion, secretion and aggregation. Recent studies suggest the existence of yet uncharacterised platelet thiol isomerase proteins. This study aimed to identify which other thiol isomerase enzymes are present in human platelets. Through the use of immunoblotting, flow cytometry, cell-surface biotinylation and gene array analysis, we report the presence of five additional thiol isomerases in human and mouse platelets and megakaryocytes, namely; ERp57, ERp72, ERp44, ERp29 and TMX3. ERp72, ERp57, ERp44 and ERp29 are released by platelets and relocate to the cell surface following platelet activation. The transmembrane thiol isomerase TMX3 was also detected on the platelet surface but does not increase following activation. Extracellular PDI is also implicated in the regulation of coagulation by the modulation of tissue factor activity. ERp57 was identified within platelet-derived microparticle fractions, suggesting that ERp57 may also be involved in the regulation of coagulation as well as platelet function. These data collectively implicate the expanding family of platelet-surface thiol isomerases in the regulation of haemostasis.
Holbrook
Lisa-Marie
LM
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Whiteknights, Reading, Berkshire.
Watkins
Nicholas A
NA
Simmonds
Alan D
AD
Jones
Chris I
CI
Ouwehand
Willem H
WH
Gibbins
Jonathan M
JM
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D006801:Humans; D008533:Megakaryocytes / Q000201:enzymology; D051379:Mice; D015539:Platelet Activation / Q000502:physiology*; D019704:Protein Disulfide-Isomerases / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013917:Thrombin / Q000494:pharmacology
D012333:RNA, Messenger; D013917:Thrombin; D019704:Protein Disulfide-Isomerases; C498879:TMX3 protein, human