High impact information on PKP4

• The armadillo protein p0071 regulates Rho signalling during cytokinesis [1].
• Both knockdown and overexpression of p0071 interfered with normal cell growth and survival due to cytokinesis defects with formation of multinucleated cells and induction of apoptosis [1].
• Deletion analysis using the yeast two-hybrid system revealed that the armadillo repeat domain of p0071 bound directly to VE-cadherin [2].
• Based on previous findings that both VE-cadherin and desmoplakin play central roles in vasculogenesis, these new results suggest that p0071 may play an important role in endothelial junction assembly and in the morphogenic events associated with vascular remodeling [2].
• Erbin binds to p0071 in vitro and in vivo in a PDZ domain-dependent manner, and both proteins colocalized in desmosomes of epithelial cells [3].

Biological context of PKP4

• Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains [4].
• We propose that Erbin is connected by p0071 to cytoskeletal networks in an interaction crucial for epithelial homeostasis [3].
• p0071, a member of the armadillo multigene family, is a constituent of sarcomeric I-bands in human skeletal muscle [5].
• During myofibrillogenesis, p0071 was not detected in non-striated nascent myofibrils, but became apparent shortly after the development of compact Z-discs in early myotubes [5].
• Here, we show that the armadillo protein p0071, unlike its relative p120(ctn), is localized at the midbody during cytokinesis and is essential for cell division [1].

Anatomical context of PKP4

• PAPIN and p0071 are ubiquitously expressed in various tissues and are localized at cell-cell junctions in normal rat kidney cells and bronchial epithelial cells [6].
• CONCLUSION: These results show that ERBIN interacts in vivo with p0071 and that it may be involved in the organization of adherens junctions and the desmosomes of epithelia [7].
• In contrast, p0071 has been described as a protein with dual localization in adherens junctions and desmosomes depending on the cell type examined [4].
• We show here that Erbin interacts with p0071 (also called plakophilin-4), an armadillo repeat protein linked to the cytoskeleton [3].
• In cells that came into contact, PAPIN was diffusely distributed on the plasma membrane, while p0071 was concentrated at immature cell-cell contacts [8].

Physical interactions of PKP4

• Endogenous ERBIN was co-immunoprecipitated with p0071 [7].
• Protein interaction studies revealed that p0071 bound to the first 160 amino-terminal residues of desmoplakin and also interacted directly with plakoglobin, suggesting that p0071 may regulate desmosome assembly by controlling plakoglobin availability [9].
• PAPIN has six PDZ domains and interacts with p0071, a catenin-related protein [8].

Co-localisations of PKP4

• At these cell-cell contact regions, ERBIN co-localizes with p0071 [7].
• In transient expression assays, p0071 colocalized with and formed complexes with both VE-cadherin and desmoplakin [2].

Other interactions of PKP4

• We also found another armadillo-protein, p0071, interacted with PS1 [10].
• ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells [7].
• In this model system, p0071 specifically enhanced adherens junction assembly but dramatically compromised desmosome assembly, resulting in keratin filament retraction from regions of cell-cell contact [9].
• We have examined whether the localization of PAPIN is determined by p0071 in epithelial cells [8].

Analytical, diagnostic and therapeutic context of PKP4

• Furthermore, we studied the expression of p0071 in a wide variety of neuromuscular disorders by indirect immunofluorescence [5].
• Northern blots revealed expression of p0071 mRNA in adult skeletal muscle tissue [5].
• RT-PCR analysis and Western blotting experiments identified two differentially spliced isoforms of p0071 [5].

References