The function of plakophilin 1 in desmosome assembly and actin filament organization.
Plakophilin 1, a member of the armadillo multigene family, is a protein with dual localization in the nucleus and in desmosomes. To elucidate its role in desmosome assembly and regulation, we have analyzed its localization and binding partners in vivo. When overexpressed in HaCaT keratinocytes, plakophilin 1 localized to the nucleus and to desmosomes, and dramatically enhanced 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. Overexpression of the armadillo repeat domain induced a striking dominant negative phenotype with the formation of filopodia and long cellular protrusions, where plakophilin 1 colocalized with actin filaments. This phenotype was strictly dependent on a conserved motif in the center of the armadillo repeat domain. Our results demonstrate that plakophilin 1 contains two functionally distinct domains: the head domain, which could play a role in organizing the desmosomal plaque in suprabasal cells, and the armadillo repeat domain, which might be involved in regulating the dynamics of the actin cytoskeleton.
Hatzfeld
M
M
Molecular Biology Group of the Medical Faculty, University of Halle, 06097 Halle/Saale, Germany. mechthild.hatzfeld@medizin.uni-halle.de
Haffner
C
C
Schulze
K
K
Vinzens
U
U
D000199:Actins / Q000378:metabolism*; D020816:Amino Acid Motifs; D000906:Antibodies / Q000276:immunology; D051186:Armadillo Domain Proteins; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000737:chemistry / Q000378:metabolism*; D029721:Drosophila Proteins; D006367:HeLa Cells; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D051191:Plakophilins; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators; D020798:Two-Hybrid System Techniques
D000199:Actins; D000906:Antibodies; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; C495297:DSG1 protein, human; C495294:DSP protein, human; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D029721:Drosophila Proteins; D019476:Insect Proteins; C495335:PKP1 protein, human; D051191:Plakophilins; D011506:Proteins; D015534:Trans-Activators; D007633:Keratins