Reactome | GPIHBP1 binds HSPG:LPL dimer

GPIHBP1 binds HSPG:LPL dimer

Stable Identifier

R-HSA-8857928

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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Lipoprotein lipase (LPL) is mainly produced by adipocytes and myocytes but is also involved in hydrolysing triglyceride-rich lipoproteins in the lumen of capillaries of heart, adipose tissue, and skeletal muscle. Heparan sulfate proteoglycan (HSPG) serves as an membrane anchor for LPL dimer but for LPL to reach its site of action in capillaries, it binds to glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), an endothelial cell membrane-bound protein. Once bound, GPIHBP1 transports LPL from within interstitial spaces, across endothelial cells to the capillary lumen (Gin et al. 2007, Young et al. 2011, Adeyo et al. 2012). Defects in GPIHBP1 can cause mislocalisation of LPL leading to severe hypertriglyceridaemia and hyperlipoproteinemia type ID (MIM:615947) (Adeyo et al. 2012, Wang & Hegele 2007, Beigneux et al. 2009, Beigneux et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
17883852	Homozygous missense mutation (G56R) in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) in two siblings with fasting chylomicronemia (MIM 144650) Wang, J, Hegele, RA	Lipids Health Dis	2007
19304573	Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase Beigneux, AP, Franssen, R, Bensadoun, A, Gin, P, Melford, K, Peter, J, Walzem, RL, Weinstein, MM, Davies, BS, Kuivenhoven, JA, Kastelein, JJ, Fong, LG, Dallinga-Thie, GM, Young, SG	Arterioscler. Thromb. Vasc. Biol.	2009
25387803	GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding Beigneux, AP, Fong, LG, Bensadoun, A, Davies, BS, Oberer, M, Gårdsvoll, H, Ploug, M, Young, SG	Circ. Res.	2015
21844202	GPIHBP1, an endothelial cell transporter for lipoprotein lipase Young, SG, Davies, BS, Voss, CV, Gin, P, Weinstein, MM, Tontonoz, P, Reue, K, Bensadoun, A, Fong, LG, Beigneux, AP	J. Lipid Res.	2011
23020258	Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 and the intravascular processing of triglyceride-rich lipoproteins Adeyo, O, Goulbourne, CN, Bensadoun, A, Beigneux, AP, Fong, LG, Young, SG	J. Intern. Med.	2012
17997385	Normal binding of lipoprotein lipase, chylomicrons, and apo-AV to GPIHBP1 containing a G56R amino acid substitution Gin, P, Beigneux, AP, Davies, B, Young, MF, Ryan, RO, Bensadoun, A, Fong, LG, Young, SG	Biochim. Biophys. Acta	2007