PRICKLE3 protects VANGL proteins from CK1-mediated phosphorylation and RNF43-mediated degradation.

ABSTRACT: The PRICKLE proteins (PRICKLE1-PRICKLE4) play essential roles in the WNT/planar cell polarity (WNT/PCP) pathway in vertebrates. This signaling system governs cell polarity, tissue architecture, and coordinated cell movements, yet the specific roles and molecular mechanisms of individual PRICKLE members within this pathway are poorly understood. Here, we identify PRICKLE3 as a previously unrecognized, central regulator of WNT/PCP signaling in human cells, Xenopus laevis and zebrafish (Danio rerio) embryos. Using enhanced proximity biotinylation (miniTurboID) combined with mass spectrometry, we found PRICKLE3 enriched at the plasma membrane, where it associates with core WNT/PCP proteins, including VANGL1 and VANGL2. Through immunoblotting, live imaging and functional assays, we further demo

SUBMITTER: Radaszkiewicz KA 

PROVIDER: S-EPMC12859043 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature