Protocadherins are new members of the cadherin superfamily. Despite the great number of protocadherin genes identified in vertebrates, little is known about their biochemical properties, functions or working mechanisms. Xenopus paraxial protocadcadherin (PAPC) was recently shown to play a role in morphogenetic cell movements during early embryonic development. However, the adhesive properties of PAPC still remain ambiguous and poorly understood, and whether its morphogenetic role is realized through its adhesive function or by other mechanisms is unclear. The long-term goals of this proposal are to elucidate the adhesive functions and mechanisms of PAPC and to understand the mechanisms of its morphogenetic activity by identifying the cytoplasmic PAPC-binding proteins. First, the adhesive properties and mechanisms, including adhesive strength, specificity, lateral dimerization and clustering, will be examined and analyzed with the cell aggregation, bead aggregation and cell attachment assays; second, the cellular localization of PAPC will be monitored to assess its role in polarized cell movements; third, the function of PAPC cytoplasmic domain, especially a highly conserved region, on the adhesive and morphogenetic activity of PAPC will be analyzed using deletion mutants; and finally, the proteins that bind PAPC cytoplasmic tail will be identified as candidates for regulation of PAPC adhesive function or PAPC-mediated signaling by means of affinity chromatography and/or the yeast two-hybrid method. The proposed research will shed light on the role of protocadherins in embryonic development and should provide important suggestions to the treatment of birth defects and other developmental diseases.
