P11. Dissecting biological functions of a Wnt/PCP pathway component Prickle

Abstract

The Wnt/planar cell polarity (PCP) pathway is one of the non-canonical Wnt signalling pathways, and known to be involved in a variety of biological processes including establishment of organised epithelia in Drosophila and regulation of grouped cell migration in vertebrate development. Prickle (Pk) belongs to the ‘core’ components of the Wnt/PCP pathway. In its N-terminal portion Pk has a PET domain, function of which is not known, and three LIM domains that are thought to be involved in protein–protein interaction. Pk is also shown to localise to the proximal side of the cells to form a complex with Vang in Drosophila PCP. However the precise mechanism by which Pk controls these biological processes remains largely unknown.To dissect and elucidate the biological functions of Pk in further detail, we have constructed a series of Pk deletion variants and tested their activities. We found that expression of a variant that lacks LIM and PET domains induces excess actin-dependent filopodia-like processes in Xenopus animal caps and HEK293 cells. This version of Pk localises to these processes. On the other hand, in animal caps expressing another variant which lacks the middle portion, cells became dissociated from each other, indicating inhibited cell adhesion. This phenotype was partially rescued by co-expression of paraxial protocadherin (PAPC).These results suggest pleiotropic roles of Pk in regulation of cytoskeleton and cell adhesion. The possible molecular interactions and mechanism underlying multiple functions of Pk will be discussed in this presentation.