HGNC Approved Gene Symbol: PPL
Cytogenetic location: 16p13.3 Genomic coordinates (GRCh38) : 16:4,882,507-4,937,148 (from NCBI)
The intermediate filament cytoskeleton of keratinocytes, composed of keratins (see 139350) that are expressed in specific expression pairs according to tissue and differentiation state, are interconnected through transmembrane protein complexes called desmosomes and connect with the basement membrane via hemidesmosomes. The proteins thought to make contact with the intermediate filaments of keratinocytes belong to a family of proteins known as plakins, of which desmoplakin (125647), envoplakin (601590), and periplakin are members. These proteins have a similar overall domain structure that includes an N-terminal globular domain, a central coiled-coil rod domain, and a C-terminal tail with characteristic repeat sequences.
Ruhrberg et al. (1997) cloned PPL from a keratinocyte expression library using antibody to PPL as the probe. The deduced 1,666-amino acid protein has a calculated molecular mass of about 205 kD. PPL shares extensive sequence homology with other proteins of the plakin family, with highest identities found in the N- and C-terminal domains. Immunoblots of keratinocyte extracts revealed a protein with an apparent molecular mass of 195 kD. Immunogold electron microscopy revealed association of PPL with the desmosomal plaque and with keratin filaments in the differentiated layers of the epidermis.
Aho et al. (1998) isolated PPL in a yeast 2-hybrid system by its interactions with type XVII collagen, a component of hemidesmosomes. The PPL clones from human keratinocyte and placenta libraries span approximately 6.2 kb. The predicted 1,756-amino acid periplakin polypeptide has a computed molecular mass of approximately 204 kD. PPL shares 50.3% amino acid sequence similarity with envoplakin. Northern blot analysis revealed that a 6.5-kb PPL message is expressed predominantly in keratinocytes compared to fibroblasts; dot blot analysis detected expression in tissues containing epithelial cells, with the highest expression in trachea, and in nonepithelial tissues, most notably in many areas of the brain.
By RT-PCR, Kazerounian et al. (2002) detected significant expression of PPL in brain, heart, liver, pancreas, placenta, skeletal muscle, colon, and small intestine.
Ruhrberg et al. (1997) noted that the influx of Ca(2+) that occurs following treatment of confluent keratinocyte cultures with a detergent or with a calcium ionophore stimulates the cross-linking of cornified envelope precursors by transglutaminases (190195). PPL became cross-linked following exposure of keratinocytes to these agents, and a transglutaminase inhibitor blocked PPL cross-linking. Coimmunoprecipitation experiments revealed interaction between PPL and envoplakin. Analysis of putative ionic interactions between the rod domains suggested that both PPL and envoplakin could form homodimers and heterodimers. Confocal immunofluorescent microscopy of cultured epidermal keratinocytes suggested that envoplakin and PPL form a network radiating from desmosomes.
Using a yeast 2-hybrid assay, Kazerounian et al. (2002) found that a linker region within the C-terminal globular domain of periplakin interacts with keratin-8 (K8; 148060) and vimentin (193060). In an in vitro pull-down assay, K18 (148070) also coprecipitated with K8 with the periplakin C-terminal tail, suggesting that periplakin can interact with K8 within the K8/K18 heterodimer.
Aho et al. (1999) determined that the PPL gene contains 22 exons and spans 60 kb. The 5-prime flanking sequence is GC rich (80%) and contains multiple AP2 (107580) and SP1 (189906) sites, but no canonical TATA or CCAAT boxes. The gene also has multiple Alu repeats and numerous MIR and L1 elements.
By radiation hybrid analysis, Aho et al. (1998) assigned the PPL gene to chromosome 16p13. By use of an interspecific backcross panel, they mapped the mouse periplakin gene to the proximal part of mouse chromosome 16, a region syntenic with human chromosome 16. By somatic cell hybrid analysis and FISH, Ruhrberg et al. (1998) mapped the PPL gene to chromosome 16p13.3. They mapped the mouse Ppl gene to chromosome 16A-B1.
Aho et al. (2004) found that Ppl -/- mice were born in the expected mendelian frequency, developed normally, possessed grossly normal epidermis and hair, and were healthy and fertile. The epidermal barrier developed normally during embryonic days 15.5 to 16.5, and the cornified envelope and desmosomes in the newborn mice were ultrastructurally normal. No compensatory increase in the expression of other epithelial proteins was detected in neonatal mouse epidermis lacking periplakin. Aho et al. (2004) concluded that the primary role of periplakin may not relate to the physiology of the cornified cell envelope in epidermal keratinocytes.
Aho, S., Li, K., Ryoo, Y., McGee, C., Ishida-Yamamoto, A., Uitto, J., Klement, J. F. Periplakin gene targeting reveals a constituent of the cornified cell envelope dispensable for normal mouse development. Molec. Cell. Biol. 24: 6410-6418, 2004. [PubMed: 15226441] [Full Text: https://doi.org/10.1128/MCB.24.14.6410-6418.2004]
Aho, S., McLean, W. H. I., Li, K., Uitto, J. cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes. Genomics 48: 242-247, 1998. [PubMed: 9521878] [Full Text: https://doi.org/10.1006/geno.1997.5188]
Aho, S., Rothenberger, K., Tan, E. M. L., Ryoo, Y. W., Cho, B. H., McLean, W. H. I., Uitto, J. Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements. Genomics 56: 160-168, 1999. [PubMed: 10051401] [Full Text: https://doi.org/10.1006/geno.1998.5704]
Kazerounian, S., Uitto, J., Aho, S. Unique role for the periplakin tail in intermediate filament association: specific binding to keratin 8 and vimentin. Exp. Derm. 11: 428-438, 2002. [PubMed: 12366696] [Full Text: https://doi.org/10.1034/j.1600-0625.2002.110506.x]
Ruhrberg, C., Hajibagheri, M. A. N., Parry, D. A. D., Watt, F. A. 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, 1997. [PubMed: 9412476] [Full Text: https://doi.org/10.1083/jcb.139.7.1835]
Ruhrberg, C., Williamson, J. A., Maatta, A., Watt, F. A. The periplakin gene maps to 16p13.3 in human and 16A-B1 in mouse. Genomics 49: 157-159, 1998. [PubMed: 9570964] [Full Text: https://doi.org/10.1006/geno.1997.5206]