Plakophilin 1, a member of the ar armadillo multigene family, is a protein
with dual localization in the nucleus and in desmosomes. To elucidate its r
ole in desmosome assembly and regulation, we have analyzed its localization
and binding partners in vivo. When overexpressed in HaCaT keratinocytes, p
lakophilin 1 localized to the nucleus and to desmosomes, and dramatically e
nhanced the recruitment of desmosomal proteins to the plasma membrane. This
effect was mediated by plakophilin 1's head domain, which interacted with
desmoglein 1, desmoplakin, and keratins in the yeast two-hybrid system. Ove
rexpression of the armadillo repeat domain induced a striking dominant nega
tive pheno-type with the formation of filopodia and long cellular protrusio
ns, where plakophilin 1 colocalized with actin filaments. This phenotype wa
s strictly dependent on a conserved motif in the center of the armadillo re
peat domain. Our results demonstrate that plakophilin 1 contains two functi
onally distinct domains: the head domain, which could play a role in organi
zing the desmosomal plaque in suprabasal cells, and the armadillo repeat do
main, which might be involved in regulating the dynamics of the actin cytos
keleton.