Low-density lipoprotein receptor-related protein 5

Definition:

Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins. Activates the canonical Wnt signaling pathway that controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration. In particular, may play an important role in the development of the posterior patterning of the epiblast during gastrulation (By similarity). During bone development, regulates osteoblast proliferation and differentiation thus determining bone mass. Mechanistically, the formation of the signaling complex between Wnt ligand, frizzled receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5, stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional programs. Acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling known to be required for retinal vascular development. Plays a role in controlling postnatal vascular regression in retina via macrophage-induced endothelial cell apoptosis (By similarity).

References:

[1]. Keiko Tamai, et al. A mechanism for Wnt coreceptor activation. Mol Cell. 2004 Jan 16;13(1):149-56. [Content Brief]

[2]. Wybrich R Cnossen, et al. LRP5 variants may contribute to ADPKD. Eur J Hum Genet. 2016 Feb;24(2):237-42. [Content Brief]

[3]. M V Semënov, et al. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001 Jun 26;11(12):951-61. [Content Brief]

[4]. Y Gong, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001 Nov 16;107(4):513-23. [Content Brief]

[5]. Mikhail Semënov, et al. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005 Jul 22;280(29):26770-5. [Content Brief]

[6]. Minrong Ai, et al. Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet. 2005 Nov;77(5):741-53. [Content Brief]

[7]. Xiaofeng Li, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005 May 20;280(20):19883-7. [Content Brief]

[8]. J Mao, et al. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 2001 Apr;7(4):801-9. [Content Brief]

[9]. Lin Zhang, et al. Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy. Genet Test Mol Biomarkers. 2016 Jul;20(7):346-51. [Content Brief]

[10]. Wybrich R Cnossen, et al. Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5343-8. [Content Brief]

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