LRP5 : LDL receptor related protein 5

Description

The LRP5 (LDL receptor related protein 5) is a protein-coding gene located on chromosome 11.

The LRP5 gene provides instructions for making a protein that is embedded in the outer membrane of many types of cells. This protein is known as a co-receptor because it works with another receptor protein, frizzled-4 (produced from the FZD4 gene), to transmit chemical signals from outside the cell to the cell's nucleus. Frizzled-4 and the LRP5 protein participate in the Wnt signaling pathway, a series of steps that affect the way cells and tissues develop. Wnt signaling is important for cell division (proliferation), attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities. The LRP5 protein plays an important role in the development and maintenance of several tissues. During early development, it helps guide the specialization of cells in the retina, which is the light-sensitive tissue that lines the back of the eye. The LRP5 protein is also involved in forming blood vessels in the retina and in the inner ear. Additionally, this protein helps regulate bone mineral density, which is a measure of the amount of calcium and other minerals in bones. The minerals give the bones strength, making them less likely to break.

LRP5 acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signals from Wnt proteins. It activates the canonical Wnt signaling pathway, which controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration. Specifically, LRP5 may play a crucial role in the posterior patterning of the epiblast during gastrulation. During bone development, LRP5 regulates osteoblast proliferation and differentiation, thereby determining bone mass. Mechanistically, the formation of a signaling complex between Wnt ligand, frizzled receptor, and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5. This stabilizes beta-catenin/CTNNB1 and activates TCF/LEF-mediated transcriptional programs. LRP5 also acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. The binding of norrin/NDP to the frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling, which is required for retinal vascular development. LRP5 plays a role in controlling postnatal vascular regression in the retina via macrophage-induced endothelial cell apoptosis.

LRP5 is also known as BMND1, EVR1, EVR4, HBM, LR3, LRP-5, LRP-7, LRP7, OPPG, OPS, OPTA1, PCLD4, VBCH2.

Associated Diseases

• Endosteal hyperostosis, Worth type
• Exudative vitreoretinopathy 4
• Isolated polycystic liver disease
• Polycystic liver disease 4 with or without kidney cysts
• Hyperostosis corticalis generalisata
• Retinopathy of prematurity
• Exudative vitreoretinopathy 1
• Hyperostosis, endosteal
• Osteopetrosis, autosomal dominant 1
• Osteoporosis-pseudoglioma syndrome
• Osteosclerosis-developmental delay-craniosynostosis syndrome
• Familial exudative vitreoretinopathy
• Juvenile primary osteoporosis