Regulatory role for the profilaggrin N-terminal domain in epidermal homeostasis.

It is well known that profilaggrin, after its release from keratohyalin granules through dephosphorylation, becomes enzymatically processed into individual filaggrin monomers. The roles for filaggrin monomers in aggregating keratin filaments, as a component of the cornified cell envelope, and as a source of natural moisturizing factor are well established. A specific N-terminal fragment, called the PF-AB domain, becomes proteolytically released as well, but much less is known about its functional role in epidermal development.

Characterization of the ubinuclein protein as a new member of the nuclear and adhesion complex components (NACos).

Background Information: We characterized previously a cellular protein through its interaction with cellular and viral transcription factors from the bZip family. The corresponding mRNA was detected in a wide range of cell types and the protein was highly expressed in the nucleus of human keratinocytes. On the basis of these observations, we named this protein ubinuclein.

Extracellular matrix protein 1 inhibits the activity of matrix metalloproteinase 9 through high-affinity protein/protein interactions.

Extracellular matrix protein 1 (ECM1), an approximately 85-kDa glycoprotein with broad tissue distribution, harbors mutations in lipoid proteinosis (LP), a heritable disease characterized by reduplication of basement membranes and hyalinization of dermis, associated with neurologic disorders. The mechanisms leading from ECM1 mutations to LP phenotype are unknown. In this study, we explored ECM1 protein-protein interactions utilizing yeast two-hybrid genetic screen of human placental library, which identified nine interacting proteins, including matrix metalloproteinase 9 (MMP9).

Breaking the connection: caspase 6 disconnects intermediate filament-binding domain of periplakin from its actin-binding N-terminal region.

Periplakin is a member of the plakin family of cytolinkers that connect cytoskeletal networks to each other as well as to the cell junctional complexes. Here, we demonstrate a direct molecular interaction between actin and periplakin. Furthermore, the oligomerization state of periplakin was shown to determine specificity of its binding to intermediate filaments (IF) in vitro.

Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases.

In epithelial cells, cell-cell and cell-matrix junctions, desmosomes and hemidesmosomes, provide anchorage sites for the keratin-intermediate filaments. The plakin proteins desmoplakin (DP), plectin, and periplakin represent intracellular constituents of these adhesion junctions. In staurosporine-treated apoptotic HaCaT cells, DP, plectin, and periplakin became cleaved coordinately with the elimination of keratins 10 and 14, while involucrin, actin, and keratin 18 displayed considerable stability.

Soluble form of Jagged1: unique product of epithelial keratinocytes and a regulator of keratinocyte differentiation.

Notch signaling pathway is an important regulator of epithelial differentiation. Recent studies have characterized multiple ligands, including Jagged1, as mediators of Notch signaling. In this work, an alternatively spliced transcript of Jagged1 was isolated in yeast two-hybrid screening through interaction with thrombospondin-1.

Periplakin gene targeting reveals a constituent of the cornified cell envelope dispensable for normal mouse development.

The members of the plakin family of proteins serve as epidermal cytolinkers and components of cell-cell and cell-matrix adhesion complexes, i.e., desmosomes and hemidesmosomes, respectively.

Many faces of periplakin: domain-specific antibodies detect the protein throughout the epidermis, explaining the multiple protein-protein interactions.

Periplakin was first identified as a precursor of the cornified cell envelope, residing in desmosomes and in interdesmosomal plasma membrane of differentiated keratinocytes in epidermis. However, most antibodies used so far have been raised against the C-terminal peptide of periplakin, the region which is heavily involved in protein-protein interactions. In order to avoid the lack of signal due to the epitope masking, other regions of periplakin were selected as antigens.

Characterization of periphilin, a widespread, highly insoluble nuclear protein and potential constituent of the keratinocyte cornified envelope.

While keratinocytes go through the terminal differentiation and move toward the outer layers of epidermis, multiple proteins become sequentially incorporated into the cornified cell envelope. We have identified through yeast two-hybrid screening a novel protein, periphilin, interacting with periplakin, which is known as a precursor of the cornified cell envelope. Periphilin gene at chromosome 12q12 gives rise to multiple alternatively spliced transcripts.

Unique role for the periplakin tail in intermediate filament association: specific binding to keratin 8 and vimentin.

Plectin, desmoplakin, and the 230-kDa bullous pemphigoid antigen (BPAG1), members of the plakin family of proteins, are multifunctional cytolinkers, connecting the cytoskeletal structures to the cell adhesion complexes. Envoplakin and periplakin are components of the cornified envelope, but less is known about their role in tissues other than the stratified epithelium. Our tissue-wide survey utilizing RT-PCR revealed that periplakin, like plectin and desmoplakin, has a wide tissue distribution, but envoplakin expression is limited to certain tissues only, and BPAG1 is clearly specific for epidermal keratinocytes.

Interspecies conservation and differential expression of mouse desmoglein gene family.

Epithelial cell adhesion is mediated by intercellular junctions, called desmosomes. Desmogleins (Dsg; Dsg1, Dsg2 and Dsg3) are calcium-dependent transmembrane adhesion components of the desmosomes. While Dsg1 and Dsg3 are mainly restricted to stratified squamous epithelia, Dsg2 is expressed in essentially all desmosome-containing epithelia.

Specific sequences in p120ctn determine subcellular distribution of its multiple isoforms involved in cellular adhesion of normal and malignant epithelial cells.

P120 catenin (p120ctn) belongs to the Armadillo family of proteins, which is implicated in cell-cell adhesion and signal transduction. Owing to alternative splicing and multiple translation initiation codons, several p120ctn isoforms can be expressed from a single gene. All p120ctn isoforms share the central Armadillo repeat domain but have divergent N- and C-termini.