Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family.
Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited by the receptor associated protein, a known ligand for members of the low density lipoprotein receptor family. Preincubation with heparin decreased the receptor binding of apolipoprotein A-V, indicating that overlap exists between the recognition sites for these receptors and for heparin. A double mutant, apolipoprotein A-V (Arg210Glu/Lys211Gln), showed decreased binding to heparin and decreased ability to bind the low density lipoprotein receptor-related protein. Association of apolipoprotein A-V with the low density lipoprotein receptor-related protein or SorLA resulted in enhanced binding of human chylomicrons to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins.
Nilsson
Stefan K
SK
Department of Medical Biosciences/Physiological Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Lookene
Aivar
A
Beckstead
Jennifer A
JA
Gliemann
Jørgen
J
Ryan
Robert O
RO
Olivecrona
Gunilla
G
D019943:Amino Acid Substitution; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000737:chemistry* / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D010949:Plasma / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D020349:Surface Plasmon Resonance
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human; D006493:Heparin; D002118:Calcium