The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors - PubMed (original) (raw)
. 1995 Jan 13;270(2):536-40.
doi: 10.1074/jbc.270.2.536.
Affiliations
- PMID: 7822276
- DOI: 10.1074/jbc.270.2.536
Free article
The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors
J D Medh et al. J Biol Chem. 1995.
Free article
Abstract
The 39-kDa receptor-associated protein (RAP) is cosynthesized and co-purifies with the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor and is thought to modulate ligand binding to LRP. In addition to binding LRP, RAP binds two other members of the low density lipoprotein (LDL) receptor family, gp330 and very low density lipoprotein (VLDL) receptors. Here, we show that RAP binds to LDL receptors as well. In normal human foreskin fibroblasts, RAP inhibited LDL receptor-mediated binding and catabolism of LDL and VLDL with Sf 20-60 or 100-400. RAP inhibited 125I-labeled LDL and Sf 100-400 lipoprotein binding at 4 degrees C with KI values of 60 and 45 nM, respectively. The effective concentrations for 50% inhibition (EC50) of cellular degradation of 2.0 nM 125I-labeled LDL, 4.7 nM 125I-labeled Sf 20-60, and 3.6 nM 125I-labeled Sf 100-400 particles were 40, 70, and 51 nM, respectively. Treatment of cells with lovastatin to induce LDL receptors increased cellular binding, internalization, and degradation of RAP by 2.3-, 1.7-, and 2.6-fold, respectively. In solid-phase assays, RAP bound to partially purified LDL receptors in a dose-dependent manner. The dissociation constant (KD) of RAP binding to LDL receptors in the solid-phase assay was 250 nM, which is higher than that for LRP, gp330, or VLDL receptors in similar assays by a factor of 14 to 350. Also, RAP inhibited 125I-labeled LDL and Sf 100-400 VLDL binding to LDL receptors in solid-phase assays with KI values of 140 and 130 nM, respectively. Because LDL bind via apolipoprotein (apo) B100 whereas VLDL bind via apoE, our results show that RAP inhibits LDL receptor interactions with both apoB100 and apoE. These studies establish that RAP is capable of binding to LDL receptors and modulating cellular catabolism of LDL and VLDL by this pathway.
Similar articles
- The 39-kDa receptor-associated protein regulates ligand binding by the very low density lipoprotein receptor.
Battey FD, Gåfvels ME, FitzGerald DJ, Argraves WS, Chappell DA, Strauss JF 3rd, Strickland DK. Battey FD, et al. J Biol Chem. 1994 Sep 16;269(37):23268-73. J Biol Chem. 1994. PMID: 8083232 - Lipoprotein lipase binds to low density lipoprotein receptors and induces receptor-mediated catabolism of very low density lipoproteins in vitro.
Medh JD, Bowen SL, Fry GL, Ruben S, Andracki M, Inoue I, Lalouel JM, Strickland DK, Chappell DA. Medh JD, et al. J Biol Chem. 1996 Jul 19;271(29):17073-80. doi: 10.1074/jbc.271.29.17073. J Biol Chem. 1996. PMID: 8663292 - The significance of apolipoprotein E structure to the metabolism of plasma triglyceride-rich lipoproteins.
Dergunov AD, Rosseneu M. Dergunov AD, et al. Biol Chem Hoppe Seyler. 1994 Aug;375(8):485-95. doi: 10.1515/bchm3.1994.375.8.485. Biol Chem Hoppe Seyler. 1994. PMID: 7811390 Review. - Lipoprotein receptors--an evolutionarily ancient multifunctional receptor family.
Dieckmann M, Dietrich MF, Herz J. Dieckmann M, et al. Biol Chem. 2010 Nov;391(11):1341-63. doi: 10.1515/BC.2010.129. Biol Chem. 2010. PMID: 20868222 Free PMC article. Review.
Cited by
- Cholesteryl ester transfer protein (CETP) expression enhances HDL cholesteryl ester liver delivery, which is independent of scavenger receptor BI, LDL receptor related protein and possibly LDL receptor.
Zhou H, Li Z, Silver DL, Jiang XC. Zhou H, et al. Biochim Biophys Acta. 2006 Dec;1761(12):1482-8. doi: 10.1016/j.bbalip.2006.09.008. Epub 2006 Sep 20. Biochim Biophys Acta. 2006. PMID: 17055779 Free PMC article. - Postprandial triglyceride-rich lipoproteins induce hepatic insulin resistance in HepG2 cells independently of their receptor-mediated cellular uptake.
Tatarczyk T, Ciardi C, Niederwanger A, Kranebitter M, Patsch JR, Pedrini MT. Tatarczyk T, et al. Mol Cell Endocrinol. 2011 Aug 22;343(1-2):71-8. doi: 10.1016/j.mce.2011.06.008. Epub 2011 Jun 15. Mol Cell Endocrinol. 2011. PMID: 21704120 Free PMC article. - Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells.
Bian Z, Shi L, Guo YL, Lv Z, Tang C, Niu S, Tremblay A, Venkataramani M, Culpepper C, Li L, Zhou Z, Mansour A, Zhang Y, Gewirtz A, Kidder K, Zen K, Liu Y. Bian Z, et al. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5434-43. doi: 10.1073/pnas.1521069113. Epub 2016 Aug 30. Proc Natl Acad Sci U S A. 2016. PMID: 27578867 Free PMC article. - Endocytic trafficking of megalin/RAP complexes: dissociation of the complexes in late endosomes.
Czekay RP, Orlando RA, Woodward L, Lundstrom M, Farquhar MG. Czekay RP, et al. Mol Biol Cell. 1997 Mar;8(3):517-32. doi: 10.1091/mbc.8.3.517. Mol Biol Cell. 1997. PMID: 9188102 Free PMC article. - Apolipoprotein C-I is an APOE genotype-dependent suppressor of glial activation.
Cudaback E, Li X, Yang Y, Yoo T, Montine KS, Craft S, Montine TJ, Keene CD. Cudaback E, et al. J Neuroinflammation. 2012 Aug 10;9:192. doi: 10.1186/1742-2094-9-192. J Neuroinflammation. 2012. PMID: 22883744 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous