Periplakin, a Novel Component of Cornified Envelopes and Desmosomes That Belongs to the Plakin Family and Forms Complexes with Envoplakin

Abstract

The cornified envelope is a layer of transglutaminase cross-linked protein that is assembled under the plasma membrane of keratinocytes in the outermost layers of the epidermis. We have determined the cDNA sequence of one of the proteins that becomes incorporated into the cornified envelope of cultured epidermal keratinocytes, a protein with an apparent molecular mass of 195 kD that is encoded by a mRNA with an estimated size of 6.3 kb. The protein is expressed in keratinizing and nonkeratinizing stratified squamous epithelia and in a number of other epithelia. Expression of the protein is upregulated during the terminal differentiation of epidermal keratinocytes in vivo and in culture. Immunogold electron microscopy was used to demonstrate an association of the 195-kD protein with the desmosomal plaque and with keratin filaments in the differentiated layers of the epidermis. Sequence analysis showed that the 195-kD protein is a member of the plakin family of proteins, to which envoplakin, desmoplakin, bullous pemphigoid antigen 1, and plectin belong. Envoplakin and the 195-kD protein coimmunoprecipitate. Analysis of their rod domain sequences suggests that the formation of both homodimers and heterodimers would be energetically favorable. Confocal immunofluorescent microscopy of cultured epidermal keratinocytes revealed that envoplakin and the 195-kD protein form a network radiating from desmosomes, and we speculate that the two proteins may provide a scaffolding onto which the cornified envelope is assembled. We propose to name the 195-kD protein periplakin.

Direct interaction between FcγRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity

“…1D), which is 32% identical and 56% similar in the proximal part of Fc␥RI-CY. Furthermore, we confirmed the capacity of PPL to form homodimers as has been suggested (14). The topology of PPL and location of the five clones identified by yeast two-hybrid screens are indicated in Fig.…”

“…Plakins contribute to the structural integrity of epithelia by, e.g., tethering cytoplasmic domains of adhesive receptors to the cytoskeleton. PPL is associated with desmosomes in keratinocytes and is involved in cornified envelope assembly (14)(15)(16)). PPL's central rod domain mediates homo-and heterodimerization and separates the N terminus (which can associate with actin filaments) from the vimentin-interacting C terminus (17)(18)(19).…”

Bricks and mortar of the epidermal barrier

“…However, the sites of isopeptide bond formation were not identified in them, and the conclusion that they are in fact integral CE components awaits verification. Two other proteins, envoplakin and periplakin, which are structural homologues of desmoplakin, are located at or between the desmosome junctions of stratified squamous epithelia (Ruhrberg e t al., 1996;Ruhrberg et al, 1997). These become crosslinked components of mature CEs, and indeed, envoplakin seems to mediate linkages between desmoplakin and KIF Candi et al, 1998a).…”

Structure and Regulation of the Envoplakin Gene

“…Envoplakin and periplakin are also found in desmosomes, and it has been proposed that they act as an interdesmosomal scaffold on which the cornified envelope is assembled (13,14,17). A further contribution of envoplakin and periplakin to epidermal barrier function is the covalent attachment of ceramide lipids to these proteins (17).…”

“…The two newest members of the plakin family are envoplakin and periplakin (13)(14)(15), which were originally identified as components of the epidermal cornified envelope, a submembranous layer of transglutaminase cross-linked protein that contributes to the barrier properties of the outermost layers of the skin (16). Envoplakin and periplakin are also found in desmosomes, and it has been proposed that they act as an interdesmosomal scaffold on which the cornified envelope is assembled (13,14,17).…”