The function of plakophilin 1 in desmosome assembly and actin filament organization

Citation
M. Hatzfeld et al., The function of plakophilin 1 in desmosome assembly and actin filament organization, J CELL BIOL, 149(1), 2000, pp. 209-222
Citations number
59
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
00219525 → ACNP
Volume
149
Issue
1
Year of publication
2000
Pages
209 - 222
Database
ISI
SICI code
0021-9525(20000403)149:1<209:TFOP1I>2.0.ZU;2-3
Abstract
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.