Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.
Background References
1. Semenov M V et al. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol 11:951-961 (2001).
2. Hao H.X et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 485:195-200 (2012).
Sequence Similarity
Belongs to the G-protein coupled receptor Fz/Smo family.
Tissue Specificity
Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.
Post-translational Modification
Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.
Immunohistochemical analysis of paraffin-embedded human uterus tissue using anti-Frizzled 8 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET7107-68, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded human kidney tissue using anti-Frizzled 8 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET7107-68, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Western blot analysis of Frizzled 8 on different lysates with Rabbit anti-Frizzled 8 antibody (ET7107-68) at 1/1,000 dilution.
Lane 1: mouse lung tissue lysate
Lysates/proteins at 20 µg/Lane. Exposure time: 3 minutes; ECL: K1801
Blocking: 5% NFDM/TBST, 1 hour at room temperature Primary antibody: ET7107-68, 1/1,000 in primary antibody dilution buffer (K1803), overnight at 4 ℃ Secondary antibody: Goat anti-Rabbit IgG-HRP (HA1001), 1/50,000 in 5% NFDM/TBST, 1 hour at room temperature
Predicted band size: 73 kDa Observed band size: 73 kDa
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