Xenopus paraxial protocadherin inhibits Wnt/ß-catenin signalling via casein kinase 2ß.

Xenopus paraxial protocadherin (PAPC) regulates cadherin-mediated cell adhesion and promotes the planar cell polarity (PCP) pathway. Here we report that PAPC functions in the Xenopus gastrula as an inhibitor of the Wnt/ß-catenin pathway. The intracellular domain of PAPC interacts with casein kinase 2 beta (CK2ß), which is part of the CK2 holoenzyme. The CK2α/ß complex stimulates Wnt/ß-catenin signalling, and the physical interaction of CK2ß with PAPC antagonizes this activity. By this mechanism, PAPC restricts the expression of Wnt target genes during gastrulation. These experiments identify a novel function of protocadherins as regulators of the Wnt pathway.