Mouse LRP‑6 Alexa Fluor™ Plus 405‑conjugated Antibody

The low-density lipoprotein (LDL) receptor-related protein 5 (LRP-5) and LRP-6 constitute a distinct subgroup of the LDL receptor family (1). Both LRP-5 and LRP-6 are type I transmembrane proteins that function as Wnt co-receptors with Frizzled proteins (FZD) (2, 3, 4). The mouse LRP-6 cDNA encodes a 1613 amino acid (aa) residue precursor including a 19 aa signal sequence, 1351 aa extracellular domain (ECD), a 23 aa transmembrane (TM) segment, and a 20 aa cytoplasmic domain (5). The ECD contains 20 YWTD motif-containing LDLR-B domains, fourEGF-like repeats, and three cysteine-rich LDLR-A repeats. The ECD of mouse LRP-6 shares 71% aa sequence identity with the ECD of mouse LRP-5 and 98% aa sequence identity with the ECD of human, rat, and canine LRP-6. The intracellular region of LRP-6 contains repeated PPPSP motifs. When the Ser/Thr in these motifs are phosphorylated, LRP-6 can interact with Axin and propagate canonical Wnt signal transduction (6, 7). LRP-6 forms inactive homodimers via its YWTD-EGF domains (8). Wnt binding to FZD and subsequent association with LRP-6 lead to activating conformational changes in LRP-6 cytoplasmic domains (8). LRP-6 can also interact directly with the Dickkopf (Dkk), sclerostin, and Wise proteins which are modulators of Wnt signaling (9 - 14). Formation of a ternary complex of LRP-6, Dkk-1, and Kremen triggers the internalization of the complex and removal LRP-6 from the cell surface. LRP-5 and LRP-6 share overlapping functions in diverse embryonic developmental processes (15).