Binding Preferences for GPIHBP1, a Glycosylphosphatidylinositol-Anchored Protein of Capillary Endothelial Cells

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 31; no. 1; pp. 176 - 182
• Main Authors: Gin, Peter, Beigneux, Anne P, Voss, Constance, Davies, Brandon, Beckstead, Jennifer A, Ryan, Robert O, Bensadoun, André, Fong, Loren G, Young, Stephen G
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2011; Lippincott Williams & Wilkins
• Subjects: Animals; Apolipoproteins A - metabolism; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Capillaries - cytology; Capillaries - metabolism; Cardiology. Vascular system; Carrier Proteins - genetics; Carrier Proteins - metabolism; CHO Cells; Chylomicrons - metabolism; Cricetinae; Cricetulus; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Lipoprotein Lipase - metabolism; Lipoproteins, HDL - metabolism; Medical sciences; Mutation; Protein Binding; Protein Interaction Domains and Motifs; Protein Interaction Mapping; Receptors, Lipoprotein; Recombinant Fusion Proteins - metabolism; Transfection; Vertebrates: cardiovascular system; Vascular disease; Endothelial cell; apolipoproteins; lipids; Atherosclerosis; Cardiovascular disease; Apolipoprotein; Lipoprotein; Metabolism; lipoproteins
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.110.214718

OBJECTIVE—To define the ability of GPIHBP1 to bind other lipase family members and other apolipoproteins (apos) and lipoproteins. METHODS AND RESULTS—GPIHBP1, a GPI-anchored lymphocyte antigen (Ly)6 protein of capillary endothelial cells, binds lipoprotein lipase (LPL) avidly, but its ability to bind related lipase family members has never been evaluated. As judged by cell-based and cell-free binding assays, LPL binds to GPIHBP1, but other members of the lipase family do not. We also examined the binding of apoAV-phospholipid disks to GPIHBP1. ApoAV binds avidly to GPIHBP1-transfected cells; this binding requires GPIHBP1ʼs amino-terminal acidic domain and is independent of its cysteine-rich Ly6 domain (the latter domain is essential for LPL binding). GPIHBP1-transfected cells did not bind high-density lipoprotein. Chylomicrons bind avidly to GPIHBP1-transfected Chinese hamster ovary cells, but this binding is dependent on GPIHBP1ʼs ability to bind LPL within the cell culture medium. CONCLUSION—GPIHBP1 binds LPL but does not bind other lipase family members. GPIHBP1 binds apoAV but does not bind apoAI or high-density lipoprotein. The ability of GPIHBP1-transfected Chinese hamster ovary cells to bind chylomicrons is mediated by LPL; chylomicron binding does not occur unless GPIHBP1 first captures LPL from the cell culture medium.