Envoplakine

Envoplakin is a member of the plakin family of cytoskeletal linker proteins that mediate the association of intermediate filaments with cell-cell and cell-extracellular matrix interaction sites (Määttä A et al. 2000). The common domain structure of plakins reflects this function. The N-terminal globular domain directs the proteins to membrane localization sites, desmosomes or hemidesmosomes. The central rod-shaped domain forms a coiled-coil structure and mediates the assembly of plakins into homodimers and presumably also into higher-order structures. Finally, the C-terminal globular domain binds to intermediate filament bundles.

Currently, in addition to desmoplakin, four other five members of the plakin protein family are well characterized.

• Desmoplakin is a common component of the inner desmosomal plaque and binds keratin filaments to cell-cell junctions of epithelial cells ( Kowalczyk AP et al-1999)
• Plectin ( Wiche G et al. 1991) - coding gene is PLEC - , Plectin is a ubiquitously expressed protein that can link intermediate filaments to microtubules and the actin cytoskeleton and is present in desmosomes, hemidesmosomes and adhesion contacts.
• BPAG1 (Sawamura D et al. (1991): "Human bullous pemphigoid antigen (BPAG1)" is also a component of the hemidesmosome plaque in epithelia, while splice variants of BPAG1 found in neurons bind not only neurofilaments but also actin filaments and microtubules (Yang Y et al. 1999) .
• Envoplakin and periplakin: Envoplakin and periplakin are the two newest members of the plakin family are envoplakin and periplakin. They were originally identified as components of the epidermal stratum corneum, a submembranous layer of transglutaminase cross-linked proteins that contributes to the barrier properties of the outermost layers of the skin. Envoplakin and periplakin are also found in desmosomes and are thought to act as an interdesmosomal scaffold on which the stratum corneum is built. In addition to their expression in the epidermis, envoplakin and periplakin are also found in other multilayered squamous epithelia as well as bilayered and transitional epithelia such as the mammary gland and urinary bladder (Ruhrberg C et al. 1997). Although envoplakin and periplakin share the characteristic plakin domain structure, their C-terminal domains are significantly smaller than the corresponding domains of the other plakins, and they are unique among plakins in that they have the potential to form heterodimers with each other. In humans, desmoplakin is haploinsufficient; a heterozygous null allele causes striate palmoplantar hyperkeratosis .

All plakins, including envoplakin and periplakin, are targets for autoantibodies in paraneoplastic pemphigus, a skin and mucosal blistering disease that occurs in some patients with lymphoid malignancies (Tamai K et al. 1993).

1. Määttä A et al. (2000) Structure and regulation of the envoplakin gene. J Biol Chem 275:19857-19865.
2. Kowalczyk AP et al. (1999) Desmosomes: intercellular adhesive junctions specialized for attachment of intermediate filaments. Int Rev Cytol 185:237-302.
3. Sawamura D et al. (1991) Human bullous pemphigoid antigen (BPAG1). Amino acid sequences deduced from cloned cDNAs predict biologically important peptide segments and protein domains. J Biol Chem 266:17784-17790.
4. Ruhrberg C et al. (1997) Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. J Cell Biol 139:1835-1849
5. Tamai K, Sawamura D, Do HC, Tamai Y, Li K, Uitto J. The human 230-kD bullous pemphigoid antigen gene (BPAG1). Exon-intron organization and identification of regulatory tissue specific elements in the promoter region. J Clin Invest. 1993 Aug;92(2):814-22.
6. Wiche G et al. (1991) Cloning and sequencing of rat plectin indicates a 466-kD polypeptide chain with a three-domain structure based on a central alpha-helical coiled coil. J Cell Biol 114:83-99.
7. Yang Y et al. (1999) Integrators of the cytoskeleton that stabilize microtubules. Cell 98:229-38.