title: Adhesive surface determines raft composition in platelets adhered under flow.
abstract: Adhesion to von Willebrand factor (VWF) induces platelet spreading, whereas adhesion to collagen induces aggregation. Here we report that cholesterol-rich domains (CRDs) or rafts play a critical role in clustering of receptors that control these responses. Platelets adhered to VWF and collagen show CRDs concentrated in filopodia which contain both the VWF receptor glycoprotein (GP) Ibalpha and the collagen receptor GPVI. Biochemical analysis of CRDs shows a threefold enrichment of GPIbalpha (but not GPVI) in VWF-adhered platelets and a fourfold enrichment of GPVI (but not GPIbalpha) in collagen-adhered platelets. Depletion of cholesterol (i) leaves the initial adhesion unchanged, (ii) inhibits spreading on VWF and aggregate formation on collagen, (iii) leaves filopodia formation intact, and (iv) reduces the localization in filopodia of GPIbalpha but not of GPVI. These data show that the adhesive substrate determines the composition of CRDs, and that cholesterol is crucial for redistribution of GPIbalpha but not of GPVI.
authors.affiliation: Laboratory for Thrombosis and Haemostasis, Department of Haematology, UMCU and Institute of Biomembranes, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Lier
authors.forename: F
authors.initials: F
authors.lastname: Lee
authors.forename: R W
authors.initials: RW
authors.lastname: Farndale
authors.forename: G
authors.initials: G
authors.lastname: Gorter
authors.forename: S
authors.initials: S
authors.lastname: Verhoef
authors.forename: Y
authors.initials: Y
authors.lastname: Ohno-Iwashita
authors.forename: J-W N
authors.initials: JW
authors.lastname: Akkerman
authors.forename: H F G
authors.initials: HF
authors.lastname: Heijnen
mesh_terms: D001792:Blood Platelets / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002784:Cholesterol / Q000172:deficiency / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000737:chemistry* / Q000378:metabolism; D012212:Rheology; D015398:Signal Transduction / Q000502:physiology; D013499:Surface Properties; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C094990:adhesion receptor; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D003094:Collagen; D002784:Cholesterol