Normal binding of lipoprotein lipase, chylomicrons, and apo-AV to GPIHBP1 containing a G56R amino acid substitution.
GPIHBP1 is an endothelial cell protein that serves as a platform for lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins within the capillaries of heart, adipose tissue, and skeletal muscle. The absence of GPIHBP1 causes severe chylomicronemia. A hallmark of GPIHBP1 is the ability to bind lipoprotein lipase, chylomicrons, and apolipoprotein (apo-) AV. A homozygous G56R mutation in GPIHBP1 was recently identified in two siblings with chylomicronemia, and the authors of that study suggested that the G56R substitution was responsible for the hyperlipidemia. In this study, we created a human GPIHBP1 expression vector, introduced the G56R mutation, and tested the ability of the mutant GPIHBP1 to reach the cell surface and bind lipoprotein lipase, chylomicrons, and apo-AV. Our studies revealed that the G56R substitution did not affect the ability of GPIHBP1 to reach the cell surface, nor did the amino acid substitution have any discernible effect on the binding of lipoprotein lipase, chylomicrons, or apo-AV.
Gin
Peter
P
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Beigneux
Anne P
AP
Davies
Brandon
B
Young
Madeline F
MF
Ryan
Robert O
RO
Bensadoun
André
A
Fong
Loren G
LG
Young
Stephen G
SG
D019943:Amino Acid Substitution; D000818:Animals; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000378:metabolism*; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D018110:Receptors, Lipoprotein
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D002352:Carrier Proteins; D002914:Chylomicrons; C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase; D005998:Glycine