Recombinant Mouse LRP-5 Protein

The low-density lipoprotein (LDL) receptor-related proteins LRP-5 and LRP-6 (LRP-5/6) constitute a distinct subgroup of the LDL receptor family (1). Both are widely expressed type I transmembrane proteins that function as Wnt co-receptors with Frizzled proteins in the beta -catenin (canonical) signaling pathway. Both also play critical roles in gastrulation and skeletal patterning during development (1-5). The 1614 amino acid (aa) mouse LRP5 contains a 30 aa signal sequence, a 1353 aa extracellular domain (ECD) with four beta -propeller structures, a 23 aa transmembrane domain and a 208 aa cytoplasmic domain (6). The beta -propellers are formed of five LDLR class B domains each, separated by EGF-like motifs, and followed by three cysteine-rich LDLR class A domains (6, 7). The ECD of mouse LRP-5 shares 95%, 99% and 71% aa sequence identity with the ECD of human LRP-5, rat LRP-5, and mouse LRP-6, respectively. LRP-5/6 associates with Wnt/Frizzled complexes, triggering phosphorylation of its intracellular PPPS motifs, binding of Axin, and propagation of beta -catenin signals (1, 7, 8). The LRP-5 ECD can also interact directly with inhibitors, such as Dickkopf (Dkk), Sclerostin, and USAG1/Wise, and the non-Wnt, activating complex of Norrin with Frizzled-4 (2, 7, 9-12). Formation of a ternary complex of LRP-5, Dkk-1, and Kremen triggers the internalization of the complex (1, 2). LRP-5/6 share many, but not all interactions (1, 2). However, deletion of LRP‑6 has a larger effect on embryonic developmental processes, while deletion and polymorphisms of LRP-5 mainly affect bone density (1, 4, 5, 9, 10). In humans, or mouse models, autosomal recessive osteoporosis-pseudoglioma syndrome and hereditary high bone mass (HBM) are caused by loss- and gain-of-function mutations LRP-5, respectively (4, 9, 10, 13). In mice, Wnt/LRP-5 may inhibit duodenal synthesis of the bone antagonist, serotonin, indirectly enhancing bone formation (14). Accordingly, serum serotonin is decreased in human HBM compared to controls (13). 

• LRP-5 Antibodies
• LRP-5 Proteins
• LRP-5 Proteins and Enzymes