Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling

Molecular and Cellular Biology

Volumn 25, Issue 12, 2005, Pages 4946-4955

  Ai, Minrong ^a   Holmen, Sheri L ^b   Van Hul, Wim ^c   Williams, Bart O ^b   Warman, Matthew L ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VAN ANDEL RESEARCH INSTITUTE   (United States)

^c ANTWERP UNIVERSITY HOSPITAL   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; LIGAND; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; MUTANT PROTEIN; PROTEIN DKK1; UNCLASSIFIED DRUG; WNT PROTEIN; WNT1 PROTEIN; WNT3A PROTEIN;

ANIMAL CELL; ARTICLE; AUTOSOMAL RECESSIVE DISORDER; BONE MASS; CELL SURFACE; CONTROLLED STUDY; ENZYME INHIBITION; FAMILIAL DISEASE; GENE EXPRESSION; GENE FUNCTION; HETEROZYGOSITY; HUMAN; HUMAN CELL; MISSENSE MUTATION; NONHUMAN; NORRIE DISEASE; OSTEOPOROSIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RAT; RECEPTOR UPREGULATION; SIGNAL TRANSDUCTION;

ANIMALS; BONE DISEASES; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LDL-RECEPTOR RELATED PROTEINS; MODELS, MOLECULAR; MOLECULAR CHAPERONES; MUTATION, MISSENSE; PHENOTYPE; PROTEIN STRUCTURE, TERTIARY; PROTEINS; SIGNAL TRANSDUCTION; WNT PROTEINS; WNT1 PROTEIN;

EID: 20344398197     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.25.12.4946-4955.2005     Document Type: Article

References (39)

1. Bafico, A., G. Liu, A. Yaniv, A. Gazit, and S. A. Aaronson. 2001. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat. Cell Biol. 3:683-686.
2. Bennett, C. N., K. A. Longo, W. S. Wright, L. J. Suva, T. F. Lane, K. D. Hankenson, and O. A. MacDougald. 2005. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc. Natl. Acad. Sci. USA 102:3324-3329.
3. Bodine, P. V., W. Zhao, Y. P. Kharode, F. J. Bex, A. J. Lambert, M. B. Goad, T. Gaur, G. S. Stein, J. B. Lian, and B. S. Komm. 2004. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol. Endocrinol. 18:1222-1237.
4. Boyden, L. M., J. Mao, J. Belsky, L. Mitzner, A. Farhi, M. A. Mitnick, D. Wu, K. Insogna, and R. P. Lifton. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346:1513-1521.
5. Fujino, T., H. Asaba, M. J. Kang, Y. Ikeda, H. Sone, S. Takada, D. H. Kim, R. X. Ioka, M. Ono, H. Tomoyori, M. Okubo, T. Murase, A. Kamataki, J. Yamamoto, K. Magoori, S. Takahashi, Y. Miyamoto, H. Oishi, M. Nose, M. Okazaki, S. Usui, K. Imaizumi, M. Yanagisawa, J. Sakai, and T. T. Yamamoto. 2003. Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc. Natl. Acad. Sci. USA 100:229-234.
6. Giarre, M., M. V. Semenov, and A. M. Brown. 1998. Wnt signaling stabilizes the dual-function protein beta-catenin in diverse cell types. Ann. N. Y. Acad. Sci. 857:43-55.
7. Gong, Y., R. B. Slee, N. Fukai, G. Rawadi, S. Roman-Roman, A. M. Reginato, H. Wang, T. Cundy, F. H. Glorieux, D. Lev, M. Zacharin, K. Oexle, J. Marcelino, W. Suwairi, S. Heeger, G. Sabatakos, S. Apte, W. N. Adkins, J. Allgrove, M. Arslan-Kirchner, J. A. Batch, P. Beighton, G. C. Black, R. G. Boles, L. M. Boon, C. Borrone, H. G. Brunner, G. F. Carle, B. Dallapiccola, A. De Paepe, B. Floege, M. L. Halfhide, B. Hall, R. C. Hennekam, T. Hirose, A. Jans, H. Juppner, C. A. Kim, K. Keppler-Noreuil, A. Kohlschuetter, D. LaCombe, M. Lambert, E. Lemyre, T. Letteboer, L. Peltonen, R. S. Ramesar, M. Romanengo, H. Somer, E. Steichen-Gersdorf, B. Steinmann, B. Sullivan, A. Superti-Furga, W. Swoboda, M. J. van den Boogaard, W. Van Hul, M. Vikkula, M. Votruba, B. Zabel, T. Garcia, R. Baron, B. R. Olsen, and M. L. Warman. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513-523.
8. He, X., M. Semenov, K. Tamai, and X. Zeng. 2004. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development 131:1663-1677.
9. Holmen, S. L., T. A. Giambernardi, C. R. Zylstra, B. D. Buckner-Berghuis, J. H. Resau, J. F. Hess, V. Glatt, M. L. Bouxsein, M. Ai, M. L. Warman, and B. O. Williams. 2004. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J. Bone Miner. Res. 19:2033-2040.
10. Holmen, S. L., A. Salic, C. R. Zylstra, M. W. Kirschner, and B. O. Williams. 2002. A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta-catenin-dependent signaling. J. Biol. Chem. 277: 34727-34735.
11. Holmen, S. L., C. R. Zylstra, A. Mukherjee, R. E. Sigler, M. C. Faugere, M. L. Bouxsein, L. Deng, T. L. Clemens, and B. O. Williams. Essential role of β-catenin in post natal bone acquisition. J. Biol. Chem., in press.
12. Hsieh, J. C., L. Lee, L. Zhang, S. Wefer, K. Brown, C. DeRossi, M. E. Wines, T. Rosenquist, and B. C. Holdener. 2003. Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell 112:355-367.
13. Hu, H., M. J. Hilton, X. Tu, K. Yu, D. M. Ornitz, and F. Long. 2005. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49-60.
14. Ibrahimi, O. A., A. V. Eliseenkova, A. N. Plotnikov, K. Yu, D. M. Ornitz, and M. Mohammadi. 2001. Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome. Proc. Natl. Acad. Sci. USA 98:7182-7187.
15. Jeon, H., W. Meng, J. Takagi, M. J. Eck, T. A. Springer, and S. C. Blacklow. 2001. Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair. Nat. Struct. Biol. 8:499-504.
16. Jiao, X., V. Ventruto, M. T. Trese, B. S. Shastry, and J. F. Hejtmancik. 2004. Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am. J. Hum. Genet. 75:878-884.
17. Johnson, M. L., K. Harnish, R. Nusse, and W. Van Hul. 2004. LRP5 and Wnt signaling: a union made for bone. J. Bone Miner. Res. 19:1749-1757.
18. Kato, M., M. S. Patel, R. Levasseur, I. Lobov, B. H. Chang, D. A. Glass H. C. Hartmann, L. Li, T. H. Hwang, C. F. Brayton, R. A. Lang, G. Karsenty, and L. Chan. 2002. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J. Cell Biol. 157:303-314.
19. Kelly, O. G., K. I. Pinson, and W. C. Skarnes. 2004. The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice. Development 131:2803-2815.
20. Kim, D. H., Y. Inagaki, T. Suzuki, R. X. Ioka, S. Z. Yoshioka, K. Magoori, M. J. Kang, Y. Cho, A. Z. Nakano, Q. Liu, T. Fujino, H. Suzuki, H. Sasano, and T. T. Yamamoto. 1998. A new low density lipoprotein receptor related protein, LRP5, is expressed in hepatocytes and adrenal cortex, and recognizes apolipoprotein E. J. Biochem. (Tokyo) 124:1072-1076.
21. Korinek, V., N. Barker, P. J. Morin, D. van Wichen, R. de Weger, K. W. Kinzler, B. Vogelstein, and H. Clevers. 1997. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science 275:1784-1787.
22. Li J., I. Sarosi, S. E. Morony, D. Hill, Y. Wang, W. Qiu, S. Adamu, M. Grisanti, K. Hoffmann, T. Gyuris, H. Nguyen, R. Cattley, P. J. Kostenuik, S. S. Simonet, and D. L. Lacey. 2004. Transgenic mice over-expressing Dkk-1 in osteoblasts develop osteoporosis. J. Bone Miner. Res. 19(Suppl. 1):S2-S543. Abstract 1017.)
23. Little, R. D., J. P. Carulli, R. G. Del Mastro, J. Dupuis, M. Osborne, C. Folz, S. P. Manning, P. M. Swain, S. C. Zhao, B. Eustace, M. M. Lappe, L. Spitzer, S. Zweier, K. Braunschweiger, Y. Benchekroun, X. Hu, R. Adair, L. Chee, M. G. FitzGerald, C. Tulig, A. Caruso, N. Tzellas, A. Bawa, B. Franklin, S. McGuire, X. Nogues, G. Gong, K. M. Allen, A. Anisowicz, A. J. Morales, P. T. Lomedico, S. M. Recker, P. Van Eerdewegh, R. R. Recker, and M. L. Johnson. 2002. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am. J. Hum. Genet. 70:11-19.
24. Magoori, K., M. J. Kang, M. R. Ito, H. Kakuuchi, R. X. Ioka, A. Kamataki, D. H. Kim, H. Asaba, S. Iwasaki, Y. A. Takei, M. Sasaki, S. Usui, M. Okazaki, S. Takahashi, M. Ono, M. Nose, J. Sakai, T. Fujino, and T. T. Yamamoto. 2003. Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. J. Biol. Chem. 278:11331-11336.
25. Mao, B., W. Wu, Y. Li, D. Hoppe, P. Stannek, A. Glinka, and C. Niehrs. 2001. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411:321-325.
26. Mao, J., J. Wang, B. Liu, W. Pan, G. H. Farr III, C. Flynn, H. Yuan, S. Takada, D. Kimelman, L. Li, and D. Wu. 2001. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol. Cell 7:801-809.
27. Parfitt, A. M., E. Schipani, D. S. Rao, W. Kupin, Z. H. Han, and H. Juppner. 1996. Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor: comparison with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 81:3584-3588.
28. Schipani, E., K. Kruse, and H. Juppner. 1995. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 268:98-100.
29. Semenov, M. V., K. Tamai, B. K. Brott, M. Kühl, S. Sokol, and X. He. 2001. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr. Biol. 11:951-961.
30. Sims, K. B. 14 May 2004, posting date. NDP-related retinopathies. Gene Rev. [Online.].
31. Tamai, K., M. Semenov, Y. Kato, R. Spokony, C. Liu, Y. Katsuyama, F. Hess, J. P. Saint-Jeannet, and X. He. 2000. LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530-535.
32. Tian, E., F. Zhan, R. Walker, E. Rasmussen, Y. Ma, B. Barlogie, and J. D. Shaughnessy, Jr. 2003. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N. Engl. J. Med. 349:2483-2494.
33. Toomes, C., H. M. Bottomley, R. M. Jackson, K. V. Towns, S. Scott, D. A. Mackey, J. E. Craig, L. Jiang, Z. Yang, R. Trerobath, G. Woodruff, C. Y. Gregory-Evans, K. Gregory-Evans, M. J. Parker, G. C. Black, L. M. Downey, K. Zhang, and C. F. Inglehearn. 2004. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am. J. Hum. Genet. 74:721-730.
34. Van Wesenbeeck, L., E. Cleiren, J. Gram, R. K. Beals, O. Benichou, D. Scopelliti, L. Key, T. Renton, C. Bartels, Y. Gong, M. L. Warman, M. C. De Vernejoul, J. Bollerslev, and W. Van Hul. 2003. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am. J. Hum. Genet. 72:763-771.
35. Wehrli, M., S. T. Dougan, K. Caldwell, L. O'Keefe, S. Schwartz, D. Vaizel-Ohayon, E. Schejter, A. Tomlinson, and S. DiNardo. 2000. arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407: 527-530.
36. Whyte, M. P., W. H. Reinus, and S. Mumm. 2004. High-bone-mass disease and LRP5. N. Engl. J. Med. 350:2096-2099.
37. Xu, Q., Y. Wang, A. Dabdoub, P. M. Smallwood, J. Williams, C. Woods, M. W. Kelley, L. Jiang, W. Tasman, K. Zhang, and J. Nathans. 2004. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116:883-895.
38. Yu, K., A. B. Herr, G. Waksman, and D. M. Ornitz. 2000. Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome. Proc. Natl. Acad. Sci. USA 97:14536-14541.
39. Zhang, Y., Y. Wang, X. Li, J. Zhang, J. Mao, Z. Li, J. Zheng, L. Li, S. Harris, and D. Wu. 2004. The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd. Mol. Cell. Biol. 24:4677-4684.