Physical and functional interaction between cell-surface calreticulin and the collagen receptors integrin alpha2beta1 and glycoprotein VI in human platelets.
Calreticulin is an abundant protein in the endoplasmic reticulum of most cells. In this study, flow cytometry and immunoprecipitation from surface-biotinylated platelets each provided direct evidence that calreticulin is also expressed on the surface of human platelets. Anti-calreticulin antibodies caused platelet activation, inducing FcgammaRIIa-independent platelet aggregation. In addition, these antibodies inhibited platelet adhesion to the integrin alpha2beta1-specific ligands, GFOGER-GPP and monomeric collagen I, and to the glycoprotein VI-specific ligand, CRP. Inhibition of platelet adhesion to these ligands was independent of integrin alphaIIbbeta3. In resting platelets, calreticulin was shown to interact with integrin alpha2beta1 and glycoprotein VI. Together, these data demonstrate that surface calreticulin is associated with collagen receptors on the platelet surface, where it may play a role in the modulation of the platelet-collagen interaction.
D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D037282:Calreticulin / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry*; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008024:Ligands; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D038981:Receptors, Collagen / Q000378:metabolism; D013915:Thrombasthenia / Q000473:pathology
D000906:Antibodies; D037282:Calreticulin; D038982:Integrin alpha2beta1; D008024:Ligands; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; D003094:Collagen