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Journal of Diabetes Research
Volume 2017, Article ID 8356537, 10 pages
https://doi.org/10.1155/2017/8356537
Review Article

The LDL Receptor-Related Protein 1: At the Crossroads of Lipoprotein Metabolism and Insulin Signaling

1Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
2Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
3Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA

Correspondence should be addressed to Selen C. Muratoglu; ude.dnalyramu.mos@ainatacs

Received 3 March 2017; Accepted 11 April 2017; Published 11 May 2017

Academic Editor: Paola Llanos

Copyright © 2017 Dianaly T. Au et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. G. M. M. Alberti, R. H. Eckel, S. M. Grundy et al., “Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity,” Circulation, vol. 120, no. 16, pp. 1640–1645, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. Centers for Disease Control and Prevention, National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014, U.S. Department of Health and Human Services, Atlanta, GA, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. I. J. Goldberg, “Diabetic dyslipidemia: causes and consequences,” The Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 3, pp. 965–971, 2001. View at Publisher · View at Google Scholar
  4. L. Li and C. Hölscher, “Common pathological processes in Alzheimer disease and type 2 diabetes: a review,” Brain Research Reviews, vol. 56, no. 2, pp. 384–402, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Herz, D. E. Clouthier, and R. E. Hammer, “LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation,” Cell, vol. 71, no. 3, pp. 411–421, 1992. View at Publisher · View at Google Scholar · View at Scopus
  6. C. Nakajima, P. Haffner, S. M. Goerke et al., “The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development,” Development, vol. 141, no. 23, pp. 4513–4525, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. S. K. Moestrup and J. Gliemann, “Purification of the rat hepatic a2-macroglobulin receptor as an approximately 440-kDa single chain protein,” The Journal of Biological Chemistry, vol. 264, no. 26, pp. 15574–15577, 1989. View at Google Scholar
  8. J. D. Ashcom, S. E. Tiller, K. Dickerson, J. L. Cravens, W. S. Argraves, and D. K. Strickland, “The human a2-macroglobulin receptor: identification of a 420-kD cell surface glycoprotein specific for the activated conformation of a2-macroglobulin,” The Journal of Cell Biology, vol. 110, no. 4, pp. 1041–1048, 1990. View at Publisher · View at Google Scholar
  9. U. Beisiegel, W. Weber, G. Ihrke, J. Herz, and K. K. Stanley, “The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein,” Nature, vol. 341, no. 6238, pp. 162–164, 1989. View at Publisher · View at Google Scholar
  10. A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland, “LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies,” Physiological Reviews, vol. 88, no. 3, pp. 887–918, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. S. L. Gonias and W. M. Campana, “LDL receptor-related protein-1: a regulator of inflammation in atherosclerosis, cancer, and injury to the nervous system,” The American Journal of Pathology, vol. 184, no. 1, pp. 18–27, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. D. K. Strickland, D. T. Au, P. Cunfer, and S. C. Muratoglu, “Low-density lipoprotein receptor-related protein-1: role in the regulation of vascular integrity,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 34, no. 3, pp. 487–498, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Herz and D. K. Strickland, “LRP: a multifunctional scavenger and signaling receptor,” The Journal of Clinical Investigation, vol. 108, no. 6, pp. 779–784, 2001. View at Publisher · View at Google Scholar
  14. M. Guttman, G. N. Betts, H. Barnes, M. Ghassemian, P. Van Der Geer, and E. A. Komives, “Interactions of the NPXY microdomains of the low density lipoprotein receptor-related protein 1,” Proteomics, vol. 9, no. 22, pp. 5016–5028, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Herz, J. L. Goldstein, D. K. Strickland, Y. K. Ho, and M. S. Brown, “39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/a2-macroglobulin receptor,” The Journal of Biological Chemistry, vol. 266, no. 31, pp. 21232–21236, 1991. View at Google Scholar
  16. S. E. Williams, J. D. Ashcom, W. S. Argraves, and D. K. Strickland, “A novel mechanism for controlling the activity of a2-macroglobulin receptor/low density lipoprotein receptor-related protein: multiple regulatory sites for 39-kDa receptor-associated protein,” The Journal of Biological Chemistry, vol. 267, no. 13, pp. 9035–9040, 1992. View at Google Scholar
  17. J. J. McCarthy, A. Parker, R. Salem et al., “Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes,” Journal of Medical Genetics, vol. 41, no. 5, pp. 334–341, 2004. View at Publisher · View at Google Scholar
  18. M. J. Bown, G. T. Jones, S. C. Harrison et al., “Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1,” American Journal of Human Genetics, vol. 89, no. 5, pp. 619–627, 2011. View at Google Scholar
  19. S. Galora, C. Saracini, G. Pratesi et al., “Association of rs1466535 LRP1 but not rs3019885 SLC30A8 and rs6674171 TDRD10 gene polymorphisms with abdominal aortic aneurysm in Italian patients,” Journal of Vascular Surgery, vol. 61, no. 3, pp. 787–792, 2015. View at Publisher · View at Google Scholar · View at Scopus
  20. D. I. Chasman, M. Schurks, V. Anttila et al., “Genome-wide association study reveals three susceptibility loci for common migraine in the general population,” Nature Genetics, vol. 43, no. 7, pp. 695–698, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Ghosh, S. Pradhan, and B. Mittal, “Genome-wide-associated variants in migraine susceptibility: a replication study from north India,” Headache, vol. 53, no. 10, pp. 1583–1594, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Delgado-Lista, P. Perez-Martinez, S. Juan et al., “Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study,” The Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 2, pp. E384–E389, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. B. Thorens and M. Mueckler, “Glucose transporters in the 21st century,” American Journal of Physiology. Endocrinology and Metabolism, vol. 298, no. 2, pp. E141–E145, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. A. R. Manolescu, K. Witkowska, A. Kinnaird, T. Cessford, and C. Cheeseman, “Facilitated hexose transporters: new perspectives on form and function,” Physiology, vol. 22, no. 4, pp. 234–240, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. H.-G. Joost, G. I. Bell, J. D. Best et al., “Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators,” American Journal of Physiology. Endocrinology and Metabolism, vol. 282, no. 4, pp. E974–E976, 2002. View at Publisher · View at Google Scholar
  26. A. De Vos, H. Heimberg, E. Quartier et al., “Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression,” The Journal of Clinical Investigation, vol. 96, no. 5, pp. 2489–2495, 1995. View at Publisher · View at Google Scholar
  27. L. J. McCulloch, M. van de Bunt, M. Braun, K. N. Frayn, A. Clark, and A. L. Gloyn, “GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus,” Molecular Genetics and Metabolism, vol. 104, no. 4, pp. 648–653, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. K. T. Coppieters, A. Wiberg, N. Amirian, T. W. Kay, and M. G. von Herrath, “Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals,” Diabetes/Metabolism Research and Reviews, vol. 27, no. 8, pp. 746–754, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. F. M. Matschinsky, “Glucokinase as glucose sensor and metabolic signal generator in pancreatic b-cells and hepatocytes,” Diabetes, vol. 39, no. 6, pp. 647–652, 1990. View at Publisher · View at Google Scholar
  30. F. C. Schuit, P. Huypens, H. Heimberg, and D. G. Pipeleers, “Glucose sensing in pancreatic b-cells: a model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus,” Diabetes, vol. 50, no. 1, pp. 1–11, 2001. View at Publisher · View at Google Scholar
  31. B. S. McEwen and L. P. Reagan, “Glucose transporter expression in the central nervous system: relationship to synaptic function,” European Journal of Pharmacology, vol. 490, no. 1–3, pp. 13–24, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. E. A. Winkler, Y. Nishida, A. P. Sagare et al., “GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration,” Nature Neuroscience, vol. 18, no. 4, pp. 521–530, 2015. View at Publisher · View at Google Scholar · View at Scopus
  33. B. Thorens, “GLUT2, glucose sensing and glucose homeostasis,” Diabetologia, vol. 58, no. 2, pp. 221–232, 2015. View at Publisher · View at Google Scholar · View at Scopus
  34. L. Orci, R. H. Unger, M. Ravazzola et al., “Reduced b-cell glucose transporter in new onset diabetic BB rats,” The Journal of Clinical Investigation, vol. 86, no. 5, pp. 1615–1622, 1990. View at Publisher · View at Google Scholar
  35. B. Thorens, G. C. Weir, J. L. Leahy, H. F. Lodish, and S. Bonner-Weir, “Reduced expression of the liver/beta-cell glucose transporter isoform in glucose-insensitive pancreatic beta cells of diabetic rats,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 17, pp. 6492–6496, 1990. View at Google Scholar
  36. S. Huang and M. P. Czech, “The GLUT4 glucose transporter,” Cell Metabolism, vol. 5, no. 4, pp. 237–252, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. U. Beisiegel, W. Weber, and G. Bengtsson-Olivecrona, “Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 19, pp. 8342–8346, 1991. View at Google Scholar
  38. J. Heeren, A. Niemeier, M. Merkel, and U. Beisiegel, “Endothelial-derived lipoprotein lipase is bound to postprandial triglyceride-rich lipoproteins and mediates their hepatic clearance in vivo,” Journal of Molecular Medicine, vol. 80, no. 9, pp. 576–584, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. P. L. S. M. Gordts, R. Nock, N.-H. Son et al., “ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors,” The Journal of Clinical Investigation, vol. 126, no. 8, pp. 2855–2866, 2016. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Gliemann, T. R. Larsen, and L. Sottrup-Jensen, “Cell association and degradation of alpha 2-macroglobulin-trypsin complexes in hepatocytes and adipocytes,” Biochimica et Biophysica Acta, vol. 756, no. 2, pp. 230–237, 1983. View at Google Scholar
  41. S. Corvera, D. F. Graver, and R. M. Smith, “Insulin increases the cell surface concentration of a2-macroglobulin receptors in 3T3-L1 adipocytes. Altered transit of the receptor among intracellular endocytic compartments,” The Journal of Biological Chemistry, vol. 264, no. 17, pp. 10133–10138, 1989. View at Google Scholar
  42. O. Descamps, D. Bilheimer, and J. Herz, “Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated a2-macroglobulin in adipocytes,” The Journal of Biological Chemistry, vol. 268, no. 2, pp. 974–981, 1993. View at Google Scholar
  43. A. Laatsch, M. Merkel, P. J. Talmud, T. Grewal, U. Beisiegel, and J. Heeren, “Insulin stimulates hepatic low density lipoprotein receptor-related protein 1 (LRP1) to increase postprandial lipoprotein clearance,” Atherosclerosis, vol. 204, no. 1, pp. 105–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Ding, X. Xian, W. L. Holland, S. Tsai, and J. Herz, “Low-density lipoprotein receptor-related protein-1 protects against hepatic insulin resistance and hepatic steatosis,” eBioMedicine, vol. 7, pp. 135–145, 2016. View at Publisher · View at Google Scholar · View at Scopus
  45. W. J. Lossow, N. Brot, and I. L. Chaikoff, “Disposition of the cholesterol moiety of a chylomicron-containing lipoprotein fraction of chyle in the rat,” Journal of Lipid Research, vol. 3, no. 2, pp. 207–215, 1962. View at Google Scholar
  46. S. M. Hofmann, L. Zhou, D. Perez-Tilve et al., “Adipocyte LDL receptor-related protein-1 expression modulates postprandial lipid transport and glucose homeostasis in mice,” The Journal of Clinical Investigation, vol. 117, no. 11, pp. 3271–3282, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. L. Nasarre, O. Juan-Babot, P. Gastelurrutia et al., “Low density lipoprotein receptor-related protein 1 is upregulated in epicardial fat from type 2 diabetes mellitus patients and correlates with glucose and triglyceride plasma levels,” Acta Diabetologica, vol. 51, no. 1, pp. 23–30, 2014. View at Publisher · View at Google Scholar · View at Scopus
  48. P. Iozzo, “Myocardial, perivascular, and epicardial fat,” Diabetes Care, vol. 34, Supplement 2, pp. S371–S379, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. M. P. Jedrychowski, C. A. Gartner, S. P. Gygi et al., “Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important vesicle component and target of insulin signaling,” The Journal of Biological Chemistry, vol. 285, no. 1, pp. 104–114, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. J. W. Slot, H. J. Geuze, S. Gigengack, G. E. Lienhard, and D. E. James, “Immuno-localization of the insulin regulatable glucose transporter in brown adipose tissue of the rat,” The Journal of Cell Biology, vol. 113, no. 1, pp. 123–135, 1991. View at Publisher · View at Google Scholar
  51. S. Y. Park, K. Y. Kim, S. Kim, and Y. S. Yu, “Affinity between TBC1D4 (AS160) phosphotyrosine-binding domain and insulin-regulated aminopeptidase cytoplasmic domain measured by isothermal titration calorimetry,” BMB Reports, vol. 45, no. 6, pp. 360–364, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. E. Loukinova, S. Ranganathan, S. Kuznetsov et al., “Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP): evidence for integrated co-receptor function between LRP and the PDGF,” The Journal of Biological Chemistry, vol. 277, no. 18, pp. 15499–15506, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. N. Bilodeau, A. Fiset, M. C. Boulanger et al., “Proteomic analysis of Src family kinases signaling complexes in golgi/endosomal fractions using a site-selective anti-phosphotyrosine antibody: identification of LRP1-insulin receptor complexes,” Journal of Proteome Research, vol. 9, no. 2, pp. 708–717, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. P. D. Brewer, E. N. Habtemichael, I. Romenskaia, C. C. Mastick, and A. C. F. Coster, “Insulin-regulated Glut4 translocation: membrane protein trafficking with six distinctive steps,” The Journal of Biological Chemistry, vol. 289, no. 25, pp. 17280–17298, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. D. J. Selkoe, “Translating cell biology into therapeutic advances in Alzheimer’s disease,” Nature, vol. 399, 6738 Supplement, pp. A23–A31, 1999. View at Publisher · View at Google Scholar
  56. B. V. Zlokovic, “Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders,” Nature Reviews. Neuroscience, vol. 12, no. 12, pp. 723–738, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. A. M. A. Brands, G. J. Biessels, E. H. F. de Haan, L. J. Kappelle, and R. P. C. Kessels, “The effects of type 1 diabetes on cognitive performance: a meta-analysis,” Diabetes Care, vol. 28, no. 3, pp. 726–735, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Janson, T. Laedtke, J. E. Parisi, P. O’Brien, R. C. Petersen, and P. C. Butler, “Increased risk of type 2 diabetes in Alzheimer disease,” Diabetes, vol. 53, no. 2, pp. 474–481, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. G. J. Biessels, S. Staekenborg, E. Brunner, C. Brayne, and P. Scheltens, “Risk of dementia in diabetes mellitus: a systematic review,” Lancet Neurology, vol. 5, no. 1, pp. 64–74, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. T. J. Nelson and D. L. Alkon, “Insulin and cholesterol pathways in neuronal function, memory and neurodegeneration,” Biochemical Society Transactions, vol. 33, no. 5, p. 1033, 2005. View at Google Scholar
  61. S. Hoyer, “Glucose metabolism and insulin receptor signal transduction in Alzheimer disease,” European Journal of Pharmacology, vol. 490, no. 1–3, pp. 115–125, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Salkovic-Petrisic, J. Osmanovic, E. Grünblatt, P. Riederer, and S. Hoyer, “Modeling sporadic Alzheimer’s disease: the insulin resistant brain state generates multiple long-term morphobiological abnormalities including hyperphosphorylated tau protein and amyloid-beta,” Journal of Alzheimer’s Disease, vol. 18, no. 4, pp. 729–750, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. R. D. Bell, R. Deane, N. Chow et al., “SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells,” Nature Cell Biology, vol. 11, no. 2, pp. 143–153, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. C.-C. Liu, J. Hu, C.-W. Tsai et al., “Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain,” The Journal of Neuroscience, vol. 35, no. 14, pp. 5851–5859, 2015. View at Publisher · View at Google Scholar · View at Scopus
  65. G. A. Werther, A. Hogg, B. J. Oldfield et al., “Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry,” Endocrinology, vol. 121, no. 4, pp. 1562–1570, 1987. View at Publisher · View at Google Scholar · View at Scopus
  66. M. W. Schwartz, D. P. Figlewicz, D. G. Baskin, S. C. Woods, and D. Porte, “Insulin in the brain: a hormonal regulator of energy balance,” Endocrine Reviews, vol. 13, no. 3, pp. 387–414, 1992. View at Publisher · View at Google Scholar · View at Scopus
  67. E. Blazquez, E. Velazquez, V. Hurtado-Carneiro, and J. M. Ruiz-Albusac, “Insulin in the brain: its pathophysiological implications for states related with central insulin resistance, type 2 diabetes and Alzheimer’s disease,” Frontiers in Endocrinology, vol. 5, p. 161, 2014. View at Publisher · View at Google Scholar · View at Scopus
  68. D. G. Baskin, L. J. Stein, H. Ikeda et al., “Genetically obese zucker rats have abnormally low brain insulin content,” Life Sciences, vol. 36, no. 7, pp. 627–633, 1985. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Luo, J. Becnel, C. D. Nichols, and D. R. Nässel, “Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor,” Cellular and Molecular Life Sciences, vol. 69, no. 3, pp. 471–484, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Brankatschk, S. Dunst, L. Nemechke, and S. Eaton, “Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling,” eLife, vol. 3, p. e02862, 2014. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Ranganathan, C. Liu, M. M. Migliorini et al., “Serine and threonine phosphorylation of the low density lipoprotein receptor-related protein by protein kinase Cα regulates endocytosis and association with adaptor molecules,” The Journal of Biological Chemistry, vol. 279, no. 39, pp. 40536–40544, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. K. W. S. Ko, R. S. Mcleod, R. K. Avramoglu et al., “Mutation at the processing site of chicken low density lipoprotein receptor-related protein impairs efficient endoplasmic reticulum exit, but proteolytic cleavage is not essential for its endocytic functions,” The Journal of Biological Chemistry, vol. 273, no. 43, pp. 27779–27785, 1998. View at Publisher · View at Google Scholar · View at Scopus