Lrp6

Summary

Gene Symbol: Lrp6
Description: low density lipoprotein receptor-related protein 6
Alias: C030016K15Rik, ska26, ska, skax26, low-density lipoprotein receptor-related protein 6, LRP-6, crooked, low density lipoprotein receptor-related protein 6; low density lipoprotein-related protein 6, low density lipoprotein-related protein 6
Species: mouse
Products:     Lrp6

Top Publications

  1. Bilic J, Huang Y, Davidson G, Zimmermann T, Cruciat C, Bienz M, et al. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science. 2007;316:1619-22 pubmed
    ..mechanism by which Wnt binding to its receptors Frizzled and Low-density lipoprotein receptor-related protein 6 (LRP6) triggers downstream signaling events...
  2. Brown S, Twells R, Hey P, Cox R, Levy E, Soderman A, et al. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem Biophys Res Commun. 1998;248:879-88 pubmed
    ..This gene, termed LDL receptor-related protein 6 (LRP6), encodes a transmembrane protein which has 71% identity and is structurally similar to the protein encoded by LRP5,..
  3. Wei W, Lu Q, Chaudry G, Leppla S, Cohen S. The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin. Cell. 2006;124:1141-54 pubmed
    ..Here we show that low density lipoprotein receptor-related protein 6 (LRP6), previously known to be a coreceptor for the Wnt signaling pathway, is required for anthrax toxin lethality in ..
  4. Semenov M, Zhang X, He X. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem. 2008;283:21427-32 pubmed publisher
    ..DKK1 is a high affinity antagonistic ligand for LRP6, which is a Wnt coreceptor that acts together with the Frizzled serpentine receptor to initiate Wnt signal ..
  5. Bryja V, Andersson E, Schambony A, Esner M, Bryjova L, Biris K, et al. The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo. Mol Biol Cell. 2009;20:924-36 pubmed publisher
    ..Here, we examined the possible participation of Lrp5/6 in noncanonical Wnt signaling. We found that Lrp6 physically interacts with Wnt5a, but that this does not lead to phosphorylation of Lrp6 or activation of the Wnt/..
  6. Brennan K, González Sancho J, Castelo Soccio L, Howe L, Brown A. Truncated mutants of the putative Wnt receptor LRP6/Arrow can stabilize beta-catenin independently of Frizzled proteins. Oncogene. 2004;23:4873-84 pubmed
    ..Consistent with other reports, we find that LRP6/Arrow proteins deleted for their extracellular domain are able to activate the Wnt/beta-catenin signaling pathway...
  7. Kokubu C, Heinzmann U, Kokubu T, Sakai N, Kubota T, Kawai M, et al. Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis. Development. 2004;131:5469-80 pubmed
    Here, we present evidence that Lrp6, a coreceptor for Wnt ligands, is required for the normal formation of somites and bones...
  8. Castelo Branco G, Andersson E, Minina E, Sousa K, Ribeiro D, Kokubu C, et al. Delayed dopaminergic neuron differentiation in Lrp6 mutant mice. Dev Dyn. 2010;239:211-21 pubmed publisher
    ..The low density lipoprotein receptor-related protein (Lrp6) is a Wnt co-receptor, yet it remains unclear whether Lrp6 is required for DA neuron development or VM ..
  9. Wan M, Li J, Herbst K, Zhang J, Yu B, Wu X, et al. LRP6 mediates cAMP generation by G protein-coupled receptors through regulating the membrane targeting of G?(s). Sci Signal. 2011;4:ra15 pubmed publisher
    ..We found that the transmembrane receptor low-density lipoprotein receptor-related protein 6 (LRP6), a co-receptor for Wnt proteins, bound to the G?(s)?? heterotrimer and that knockdown of LRP6 attenuated cAMP ..

More Information

Publications86

  1. Holmen S, Giambernardi T, Zylstra C, Buckner Berghuis B, Resau J, Hess J, et al. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res. 2004;19:2033-40 pubmed
    Humans and mice lacking Lrp5 have low BMD. To evaluate whether Lrp5 and Lrp6 interact genetically to control bone or skeletal development, we created mice carrying mutations in both Lrp5 and the related gene Lrp6...
  2. Zhou C, Pinson K, Pleasure S. Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants. J Neurosci. 2004;24:7632-9 pubmed
    Mice with mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein-6 (LRP6) have a smaller and severely disorganized dorsal thalamus and lack thalamocortical projections...
  3. Kelly O, Pinson K, Skarnes W. The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice. Development. 2004;131:2803-15 pubmed
    Recent work has identified LDL receptor-related family members, Lrp5 and Lrp6, as co-receptors for the transduction of Wnt signals...
  4. Van Wesenbeeck L, Cleiren E, Gram J, Beals R, Benichou O, Scopelliti D, et al. 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. 2003;72:763-71 pubmed
    ..Functional analysis of the effects of the various mutations will be of interest, to evaluate whether all the mutations give rise to the same pathogenic mechanism. ..
  5. Maretto S, Cordenonsi M, Dupont S, Braghetta P, Broccoli V, Hassan A, et al. Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc Natl Acad Sci U S A. 2003;100:3299-304 pubmed
    ..In summary, BAT-gal mice unveil the entire complexity of Wntbeta-catenin signaling in mammals and have broad application potentials for the identification of Wnt-responsive cell populations in development and disease. ..
  6. Liu W, Mani S, Davis N, Sarrafzadegan N, Kavathas P, Mani A. Mutation in EGFP domain of LDL receptor-related protein 6 impairs cellular LDL clearance. Circ Res. 2008;103:1280-8 pubmed publisher
    Mutation in the EGFP domain of LDL receptor-related protein 6 (LRP6(R611C)) is associated with hypercholesterolemia and early-onset atherosclerosis, but the mechanism by which it causes disease is not known...
  7. Bourhis E, Tam C, Franke Y, Bazan J, Ernst J, Hwang J, et al. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010;285:9172-9 pubmed publisher
    ..this report we describe insect cell expression and purification of soluble mouse Fz8 cysteine-rich domain and human LRP6 extracellular domain and show that they inhibit Wnt/beta-catenin signaling in cellular assays...
  8. Lindvall C, Zylstra C, Evans N, West R, Dykema K, Furge K, et al. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS ONE. 2009;4:e5813 pubmed publisher
    Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such signals play central roles during development and in disease...
  9. Sato A, Yamamoto H, Sakane H, Koyama H, Kikuchi A. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29:41-54 pubmed publisher
    ..As another action of Wnt5a, it inhibited Wnt3a-dependent lipoprotein receptor-related protein 6 (LRP6) phosphorylation and beta-catenin accumulation...
  10. Khan Z, Vijayakumar S, de la Torre T, Rotolo S, Bafico A. Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor. Mol Cell Biol. 2007;27:7291-301 pubmed
    ..The LRP6 single-span transmembrane coreceptor is essential for transmission of canonical Wnt signaling...
  11. Zhong Z, Baker J, Zylstra Diegel C, Williams B. Lrp5 and Lrp6 play compensatory roles in mouse intestinal development. J Cell Biochem. 2012;113:31-8 pubmed publisher
    Low-density lipoprotein receptor-related proteins 5 and 6 (Lrp5 and Lrp6) are co-receptors of Wnt ligands and play important roles in Wnt/?-catenin signal transduction...
  12. Pinson K, Brennan J, Monkley S, Avery B, Skarnes W. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature. 2000;407:535-8 pubmed
    ..Here we present evidence that a new member of the low-density lipoprotein (LDL)-receptor-related protein family, LRP6 (ref. 3), is critical for Wnt signalling in mice...
  13. Nam J, Turcotte T, Smith P, Choi S, Yoon J. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem. 2006;281:13247-57 pubmed
    ..binding of Wnt ligands to the Frizzled (Fzd) receptor and the low density lipoprotein-related receptor (LRP) 5 or LRP6 coreceptor initiates downstream signaling events leading to gene activation by beta-catenin and the T-cell factor (..
  14. Ellies D, Viviano B, McCarthy J, Rey J, Itasaki N, Saunders S, et al. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006;21:1738-49 pubmed
    ..Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway...
  15. Lin S, Li B, Rao S, Yeo E, Hudson T, Nowlin B, et al. Macrophage Wnt7b is critical for kidney repair and regeneration. Proc Natl Acad Sci U S A. 2010;107:4194-9 pubmed publisher
  16. Joeng K, Schumacher C, Zylstra Diegel C, Long F, Williams B. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol. 2011;359:222-9 pubmed publisher
    ..is indispensable for embryonic osteoblast differentiation, the roles of the key Wnt co-receptors Lrp5 and Lrp6 are unclear...
  17. Jiang Y, He X, Howe P. Disabled-2 (Dab2) inhibits Wnt/?-catenin signalling by binding LRP6 and promoting its internalization through clathrin. EMBO J. 2012;31:2336-49 pubmed publisher
    ..Wnt signalling requires caveolin-dependent internalization of low-density lipoprotein receptor-related protein 6 (LRP6)...
  18. Kubota T, Michigami T, Sakaguchi N, Kokubu C, Suzuki A, Namba N, et al. Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd. J Bone Miner Res. 2008;23:1661-71 pubmed publisher
    ..Because roles of LRP6, another co-receptor for Wnts, in postnatal bone metabolism have not been fully elucidated, we studied bone ..
  19. Huang X, Langelotz C, Hetfeld Pechoc B, Schwenk W, Dubiel W. The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15. J Mol Biol. 2009;391:691-702 pubmed publisher
    ..A model is provided that proposes a role of CSN-mediated deneddylation in the formation of the beta-catenin-degrading supercomplex and the protection of complex-bound APC via CSN-associated USP15. ..
  20. Yang J, Mowry L, Nejak Bowen K, Okabe H, Diegel C, Lang R, et al. ?-catenin signaling in murine liver zonation and regeneration: a Wnt-Wnt situation!. Hepatology. 2014;60:964-76 pubmed publisher
    ..Hepatocytes, cholangiocytes, or macrophages are not the source of Wnts in regulating hepatic zonation. However, Kupffer cells are a major contributing source of Wnt secretion necessary for ?-catenin activation during LR. ..
  21. Porntaveetus T, Ohazama A, Choi H, Herz J, Sharpe P. Wnt signaling in the murine diastema. Eur J Orthod. 2012;34:518-24 pubmed publisher
    ..The expression of Wnt6 and Wnt11 was found in both tissues. The Wnt co-receptor, Lrp6, was weakly expressed in the diastema overlapping with weak Lrp4 expression, a co-receptor that inhibits Wnt ..
  22. Wang X, Adhikari N, Li Q, Hall J. LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2004;287:H2376-83 pubmed
    Initial studies have established expression of low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) in vascular smooth muscle cells (VSMCs)...
  23. Badders N, Goel S, Clark R, Klos K, Kim S, Bafico A, et al. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage. PLoS ONE. 2009;4:e6594 pubmed publisher
    ..Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion...
  24. Sugiyama Y, Shelley E, Wen L, Stump R, Shimono A, Lovicu F, et al. Sfrp1 and Sfrp2 are not involved in Wnt/?-catenin signal silencing during lens induction but are required for maintenance of Wnt/?-catenin signaling in lens epithelial cells. Dev Biol. 2013;384:181-93 pubmed publisher
    ..Lenses that formed in DKO mice were smaller than controls and exhibited a deficient epithelium. Thus Sfrps play a role in lens development, at least in part, by regulating aspects of Wnt/?-catenin signaling in lens epithelial cells. ..
  25. Schlossman S, Boumsell L, Gilks W, Harlan J, Kishimoto T, Morimoto C, et al. CD antigens 1993. Immunol Today. 1994;15:98-9 pubmed
  26. Szabó N, Zhao T, Cankaya M, Stoykova A, Zhou X, Alvarez Bolado G. Interaction between axons and specific populations of surrounding cells is indispensable for collateral formation in the mammillary system. PLoS ONE. 2011;6:e20315 pubmed publisher
    ..in several mouse lines carrying mutant alleles of genes expressed in defined subpopulations (including Pax6, Foxb1, Lrp6 and Gbx2) together with the use of an unambiguous genetic marker of mammillary axons revealed: 1) a specific group ..
  27. Zhou Y, Wang Y, TISCHFIELD M, Williams J, Smallwood P, Rattner A, et al. Canonical WNT signaling components in vascular development and barrier formation. J Clin Invest. 2014;124:3825-46 pubmed publisher
    ..The closely related WNT signaling coreceptors LDL receptor-related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone ..
  28. Goel S, Chin E, Fakhraldeen S, Berry S, Beebe D, Alexander C. Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts. J Biol Chem. 2012;287:16454-66 pubmed publisher
    ..However, previous data from our laboratory have shown that LRP5 and LRP6 are co-expressed in mammary basal cells and that LRP6 is active, leading us to question why LRP6 is insufficient to ..
  29. Zylstra C, Wan C, VanKoevering K, Sanders A, Lindvall C, Clemens T, et al. Gene targeting approaches in mice: assessing the roles of LRP5 and LRP6 in osteoblasts. J Musculoskelet Neuronal Interact. 2008;8:291-3 pubmed
  30. Hay E, Laplantine E, Geoffroy V, Frain M, Kohler T, Muller R, et al. N-cadherin interacts with axin and LRP5 to negatively regulate Wnt/beta-catenin signaling, osteoblast function, and bone formation. Mol Cell Biol. 2009;29:953-64 pubmed publisher
    ..These data indicate that a previously unrecognized N-cadherin-axin-LRP5 interaction negatively regulates Wnt/beta-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass. ..
  31. Abe T, Zhou P, Jackman K, Capone C, Casolla B, Hochrainer K, et al. Lipoprotein receptor-related protein-6 protects the brain from ischemic injury. Stroke. 2013;44:2284-2291 pubmed publisher
    Loss-of-function mutations of the lipoprotein receptor-related protein-6 (LRP6), a coreceptor in the Wingless-related integration site-?-catenin prosurvival pathway, have been implicated in myocardial ischemia and neurodegeneration...
  32. Loebel D, Studdert J, Power M, Radziewic T, Jones V, Coultas L, et al. Rhou maintains the epithelial architecture and facilitates differentiation of the foregut endoderm. Development. 2011;138:4511-22 pubmed publisher
  33. Chen H, Lin C, Lin C, Perez Olle R, Leung C, Liem R. The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Genes Dev. 2006;20:1933-45 pubmed
    ..Wnt stimulation, MACF1 appeared to be involved in the translocation and subsequent binding of the Axin complex to LRP6 at the cell membrane...
  34. Cole W, Trasler D. Gene-teratogen interaction in insulin-induced mouse exencephaly. Teratology. 1980;22:125-39 pubmed
    Heterozygotes for the mutant genes crooked (Cd) or rib fusion (Rf), crossed to either strain A/J or SWV produce mutant F1 offspring with minor skeletal defects...
  35. Ernest S, Carter M, Shao H, Hosack A, Lerner N, Colmenares C, et al. Parallel changes in metabolite and expression profiles in crooked-tail mutant and folate-reduced wild-type mice. Hum Mol Genet. 2006;15:3387-93 pubmed
    ..The basis for variable response and biomarkers that predict responsiveness are unknown. Crooked-tail (Cd) mutant mice are an important model of folate-responsive NTDs...
  36. Li J, Li C, Liang D, Lv F, Yuan T, The E, et al. LRP6 acts as a scaffold protein in cardiac gap junction assembly. Nat Commun. 2016;7:11775 pubmed publisher
    Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor in the canonical Wnt/?-catenin signalling. Here, we report the scaffold function of LRP6 in gap junction formation of cardiomyocytes...
  37. Ahn Y, Sims C, Logue J, Weatherbee S, Krumlauf R. Lrp4 and Wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating Wnt signaling. Development. 2013;140:583-93 pubmed publisher
    ..with elevated Wnt/?-catenin signaling and were rescued by reducing the dose of the Wnt co-receptor genes Lrp5 and Lrp6, or by inactivating the gene encoding ?-catenin...
  38. D Amico L, Mahajan S, Capietto A, Yang Z, Zamani A, Ricci B, et al. Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer. J Exp Med. 2016;213:827-40 pubmed publisher
    ..We establish a novel immunomodulatory role for Dkk1 in regulating tumor-induced immune suppression via targeting β-catenin in MDSCs. ..
  39. Liu X, Zhang B, McBride J, Zhou K, Lee K, Zhou Y, et al. Antiangiogenic and antineuroinflammatory effects of kallistatin through interactions with the canonical Wnt pathway. Diabetes. 2013;62:4228-38 pubmed publisher
    ..Coprecipitation and ligand-binding assays both showed that kallistatin binds to a Wnt coreceptor LRP6 with high affinity (Kd = 4.5 nmol/L)...
  40. Zhou C, Borello U, Rubenstein J, Pleasure S. Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway. Neuroscience. 2006;142:1119-31 pubmed
    ..b>LRP6 mutant mice are hypomorphic for the canonical Wnt signaling pathway and have hypoplasia of the developing neocortex...
  41. Kurumada S, Onishi A, Imai H, Ishii K, Kobayashi T, Sato S. Stage-specific association of apolipoprotein A-I and E in developing mouse retina. Invest Ophthalmol Vis Sci. 2007;48:1815-23 pubmed
    ..The present results document several new aspects of apoA-I and apoE in the developing retina. The switchover of the lipoprotein systems runs a parallel course with the differentiation. ..
  42. Snowball J, Ambalavanan M, Cornett B, Lang R, Whitsett J, Sinner D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Dev Biol. 2015;401:264-75 pubmed publisher
    ..Deletion of Lrp5 and Lrp6 receptors, which mediate Wnt/β-catenin signaling in the mesenchyme, partially recapitulated the phenotype ..
  43. Chen Z, Xu J, Ye Y, Li Y, Gong H, Zhang G, et al. Urotensin II inhibited the proliferation of cardiac side population cells in mice during pressure overload by JNK-LRP6 signalling. J Cell Mol Med. 2014;18:852-62 pubmed publisher
    ..the proliferation of CSPs by c-Jun N-terminal kinase (JNK) and low density lipoprotein receptor-related protein 6 (LRP6) signalling during pressure overload...
  44. Nadeau J. Do Gametes Woo? Evidence for Their Nonrandom Union at Fertilization. Genetics. 2017;207:369-387 pubmed publisher
  45. Jin Y, Turcotte T, Crocker A, Han X, Yoon J. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction. Dev Biol. 2011;352:1-13 pubmed publisher
    ..Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. ..
  46. Zhou C, Wang Y, Yamagami T, Zhao T, Song L, Wang K. Generation of Lrp6 conditional gene-targeting mouse line for modeling and dissecting multiple birth defects/congenital anomalies. Dev Dyn. 2010;239:318-26 pubmed publisher
    b>Lrp6 is a key coreceptor in the canonical Wnt pathway that is widely involved in tissue/organ morphogenesis. We generated a loxP-floxed Lrp6 mouse line...
  47. Sima J, Piao Y, Chen Y, Schlessinger D. Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development. Development. 2016;143:4723-4735 pubmed
    ..Furthermore, both Dkk4 and its receptor (and Wnt co-receptor) Lrp6 are direct Eda targets during MG induction...
  48. He F, Xiong W, Wang Y, Li L, Liu C, Yamagami T, et al. Epithelial Wnt/?-catenin signaling regulates palatal shelf fusion through regulation of Tgf?3 expression. Dev Biol. 2011;350:511-9 pubmed publisher
    ..Collectively, our results demonstrate an essential role for Wnt/?-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgf?3 in the MEE. ..
  49. Ha S, Stottmann R, Furley A, Beier D. A forward genetic screen in mice identifies mutants with abnormal cortical patterning. Cereb Cortex. 2015;25:167-79 pubmed publisher
  50. Carter M, Chen X, Slowinska B, Minnerath S, Glickstein S, Shi L, et al. Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6. Proc Natl Acad Sci U S A. 2005;102:12843-8 pubmed
    A cranial neural tube defect in Crooked tail (Cd) mice is prevented with prenatal dietary folic acid Cd positional cloning reveals a missense mutation of a highly conserved amino acid in the low density lipoprotein receptor-related ..
  51. Joiner D, Less K, Van Wieren E, Hess D, Williams B. Heterozygosity for an inactivating mutation in low-density lipoprotein-related receptor 6 (Lrp6) increases osteoarthritis severity in mice after ligament and meniscus injury. Osteoarthritis Cartilage. 2013;21:1576-85 pubmed publisher
    ..catenin signaling has been linked to osteoarthritis (OA), but the role of Lrp6-mediated Wnt/?-catenin signaling during OA remains unexplored...
  52. Revollo L, Kading J, Jeong S, Li J, SALAZAR V, Mbalaviele G, et al. N-cadherin restrains PTH activation of Lrp6/?-catenin signaling and osteoanabolic action. J Bone Miner Res. 2015;30:274-85 pubmed publisher
    ..hormone-related peptide receptor 1 (PTHR1) and low-density lipoprotein receptor-related protein 6 (Lrp6) is important for parathyroid hormone (PTH) signaling and anabolic action...
  53. Seo T, Sakon T, Nakazawa S, Nishioka A, Watanabe K, Matsumoto K, et al. Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which disrupts cell-cell adhesions in vitro and induces haemorrhage in vivo. FEBS J. 2017;284:1657-1671 pubmed publisher
    ..Indeed, we found that VAP1 cleaved the extracellular region of LRP6 and LRP5. This cleavage removes four inhibitory β-propeller structures, resulting in activation of LRP5/6...
  54. Ren D, Chen J, Li Z, Yan H, Yin Y, Wo D, et al. LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis. Nat Commun. 2015;6:6906 pubmed publisher
    ..Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain...
  55. Koraishy F, Silva C, Mason S, Wu D, Cantley L. Hepatocyte growth factor (Hgf) stimulates low density lipoprotein receptor-related protein (Lrp) 5/6 phosphorylation and promotes canonical Wnt signaling. J Biol Chem. 2014;289:14341-50 pubmed publisher
    ..Our results thus identify Hgf as an important transactivator of canonical Wnt signaling that is mediated by Met-stimulated, Gsk3-dependent Lrp5/6 phosphorylation. ..
  56. Young J, Bromberg White J, Zylstra C, Church J, Boguslawski E, Resau J, et al. LRP5 and LRP6 are not required for protective antigen-mediated internalization or lethality of anthrax lethal toxin. PLoS Pathog. 2007;3:e27 pubmed
    ..Recently, the low-density lipoprotein receptor-related protein LRP6 has been reported to mediate internalization and lethality of AnTx...
  57. Wang K, Zhang Y, Li X, Chen L, Wang H, Wu J, et al. Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. J Biol Chem. 2008;283:23371-5 pubmed publisher
    ..Dkk1 residues Arg(197), Ser(198), and Lys(232) are specifically involved in its binding to Kremen rather than to LRP6. These residues are localized at a surface that is at the opposite side of the LRP6-binding surface based on a ..
  58. González Sancho J, Brennan K, Castelo Soccio L, Brown A. Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol. 2004;24:4757-68 pubmed
    ..Our data also present Dvl phosphorylation as a general biochemical assay for Wnt protein function, including those Wnts that do not activate the Wnt/beta-catenin pathway. ..
  59. Uchihashi K, Nakatani T, Goetz R, Mohammadi M, He X, Razzaque M. FGF23-induced hypophosphatemia persists in Hyp mice deficient in the WNT coreceptor Lrp6. Contrib Nephrol. 2013;180:124-37 pubmed publisher
    ..cross-bred Hyp mice with mice deficient in the WNT coreceptor low-density lipoprotein receptor-related protein 6 (Lrp6) to generate Hyp and Lrp6 double mutant mice (Hyp/Lrp6)...
  60. Zhang Y, Yeh L, Zhang S, Call M, Yuan Y, Yasunaga M, et al. Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development. Development. 2015;142:3383-93 pubmed publisher
  61. Koduri V, Blacklow S. Requirement for natively unstructured regions of mesoderm development candidate 2 in promoting low-density lipoprotein receptor-related protein 6 maturation. Biochemistry. 2007;46:6570-7 pubmed
    ..MESD contains a central folded domain flanked by natively unstructured regions required to facilitate maturation of LRP6. Enforced expression of full-length human MESD promotes the secretion of soluble minireceptors derived from LRP6 ..
  62. Li Y, Chen J, Lu W, McCormick L, Wang J, Bu G. Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding. J Cell Sci. 2005;118:5305-14 pubmed
    Wnt co-receptors LRP5 and LRP6 are two members of the low-density lipoprotein receptor family...
  63. MacDonald B, Adamska M, Meisler M. Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6. Development. 2004;131:2543-52 pubmed
    ..We demonstrated interaction between Dkk1 and the Wnt coreceptors Lrp5 and Lrp6 by analysis of several types of double mutants...
  64. Cselenyi C, Jernigan K, Tahinci E, Thorne C, Lee L, Lee E. LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of beta-catenin. Proc Natl Acad Sci U S A. 2008;105:8032-7 pubmed publisher
    ..beta-catenin degradation, we focused on the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), which is required for signal transduction and is sufficient to activate Wnt signaling when overexpressed...
  65. Miyake A, Takahashi Y, Miwa H, Shimada A, Konishi M, Itoh N. Neucrin is a novel neural-specific secreted antagonist to canonical Wnt signaling. Biochem Biophys Res Commun. 2009;390:1051-5 pubmed publisher
    ..The expression pattern of Neucrin is distinct from that of any Dkk. Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues. ..
  66. Bell S, Schreiner C, Wert S, Mucenski M, Scott W, Whitsett J. R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis. Development. 2008;135:1049-58 pubmed publisher
    Herein, we demonstrate that Lrp6-mediated R-spondin 2 signaling through the canonical Wnt pathway is required for normal morphogenesis of the respiratory tract and limbs...
  67. Dai T, Zhang C, Peng F, Niu X, Hu L, Zhang Q, et al. Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease. Exp Ther Med. 2014;8:384-390 pubmed
    ..tyrosine hydroxylase (TH)-Cre transgenic mouse line was used to generate mice with the specific knockout of LRP5, LRP6 or ?-catenin in DA neurons...
  68. Hay E, Buczkowski T, Marty C, Da Nascimento S, Sonnet P, Marie P. Peptide-based mediated disruption of N-cadherin-LRP5/6 interaction promotes Wnt signaling and bone formation. J Bone Miner Res. 2012;27:1852-63 pubmed publisher
    ..The targeted competitor peptide-based strategy reported here may provide a novel approach to stimulate Wnt/?-catenin signaling that can be used for promoting osteoblast function and bone formation. ..
  69. Go G, Srivastava R, Hernandez Ono A, Gang G, Smith S, Booth C, et al. The combined hyperlipidemia caused by impaired Wnt-LRP6 signaling is reversed by Wnt3a rescue. Cell Metab. 2014;19:209-20 pubmed publisher
    ..Rare, nonconservative mutations in the Wnt coreceptor, LRP6, underlie autosomal dominant atherosclerosis, combined hyperlipidemia, and fatty liver disease...
  70. Verani R, Cappuccio I, Spinsanti P, Gradini R, Caruso A, Magnotti M, et al. Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid. J Neurochem. 2007;100:242-50 pubmed
    ..increased the expression of the Wnt antagonist Dkk-1, and induced the synthesis of the Wnt/Dkk-1 co-receptor LRP6. Recombinant Dkk-1 applied to EBs behaved like RA in inducing the expression of the neural markers nestin and ..
  71. Jing Z, Wei jie Y, Yi Feng Z. Down-regulation of Wt1 activates Wnt/β-catenin signaling through modulating endocytic route of LRP6 in podocyte dysfunction in vitro. Cell Signal. 2015;27:1772-80 pubmed publisher
    ..We also found that membrane LRP6 was increased dramatically in podocytes transfected with Wt1 siRNA compared with control siRNA, while no ..
  72. Lancaster M, Louie C, Silhavy J, Sintasath L, DeCambre M, Nigam S, et al. Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat Med. 2009;15:1046-54 pubmed publisher
    ..Finally, we show that Jbn is required in vivo for a Wnt response to injury and renal tubule repair, the absence of which triggers cystogenesis. ..
  73. Jin Y, Han X, Taketo M, Yoon J. Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and maxillary processes during upper jaw and lip development. Development. 2012;139:1821-30 pubmed publisher
    ..Our study has identified a previously unknown regulatory link between WNT9B and FGF signaling during lip and upper jaw development...
  74. Rajamannan N. The role of Lrp5/6 in cardiac valve disease: experimental hypercholesterolemia in the ApoE-/- /Lrp5-/- mice. J Cell Biochem. 2011;112:2987-91 pubmed publisher
    ..Finally gene expression for Lrp5, Lrp6, and Runx2 PCR was performed to evaluate the expression in the control and the cholesterol valves...
  75. Kim I, Pan W, Jones S, Zhang Y, Zhuang X, Wu D. Clathrin and AP2 are required for PtdIns(4,5)P2-mediated formation of LRP6 signalosomes. J Cell Biol. 2013;200:419-28 pubmed publisher
    ..Here we show that clathrin and adaptor protein 2 (AP2) were part of the LRP6 signalosomes...
  76. Bikkavilli R, Malbon C. Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2. J Cell Sci. 2012;125:2446-56 pubmed publisher
    ..We report a novel role for arginine methylation in regulating Wnt3a-stimulated LRP6 phosphorylation. G3BP2, a dishevelled-associated protein, is methylated in response to Wnt3a...
  77. Chassot A, Gregoire E, Lavery R, Taketo M, de Rooij D, Adams I, et al. RSPO1/?-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary. PLoS ONE. 2011;6:e25641 pubmed publisher
    ..Our results demonstrate that RSPO1/?-catenin signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm...