Summary: A family of related proteins that associate with cytoskeletal elements and junctional complexes at INTERCELLULAR JUNCTIONS. Plakins share a common plakin domain or a plakin repeat domain.

Top Publications

  1. Steinert P, Marekov L. Initiation of assembly of the cell envelope barrier structure of stratified squamous epithelia. Mol Biol Cell. 1999;10:4247-61 pubmed
    ..Together, these data stress the importance of juxtaposition of membranes, transglutaminases, and involucrin and envoplakin in the initiation of CE assembly of stratified squamous epithelia. ..
  2. van den Heuvel A, de Vries Smits A, Van Weeren P, Dijkers P, de Bruyn K, Riedl J, et al. Binding of protein kinase B to the plakin family member periplakin. J Cell Sci. 2002;115:3957-66 pubmed
    ..These results suggest a possible role for periplakin as a localization signal in PKB-mediated signalling. ..
  3. Groot K, Sevilla L, Nishi K, DiColandrea T, Watt F. Kazrin, a novel periplakin-interacting protein associated with desmosomes and the keratinocyte plasma membrane. J Cell Biol. 2004;166:653-9 pubmed
    ..On transfection, all three kazrin isoforms have similar subcellular distributions. We conclude that kazrin is a novel component of desmosomes that associates with periplakin. ..
  4. Kalinin A, Idler W, Marekov L, McPhie P, Bowers B, Steinert P, et al. Co-assembly of envoplakin and periplakin into oligomers and Ca(2+)-dependent vesicle binding: implications for cornified cell envelope formation in stratified squamous epithelia. J Biol Chem. 2004;279:22773-80 pubmed
  5. Aho S, McLean W, Li K, Uitto J. cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes. Genomics. 1998;48:242-7 pubmed
    ..Mapping of this gene in human and mouse will allow evaluation of periplakin as a candidate locus for disorders of epithelial fragility, with or without other phenotypes. ..
  6. Yoon K, FitzGerald P. Periplakin interactions with lens intermediate and beaded filaments. Invest Ophthalmol Vis Sci. 2009;50:1283-9 pubmed publisher
    ..This suggests that mutations in periplakin have the potential to emulate the cataract seen in lenses with defective BF proteins. ..
  7. Boczonadi V, McInroy L, Määttä A. Cytolinker cross-talk: periplakin N-terminus interacts with plectin to regulate keratin organisation and epithelial migration. Exp Cell Res. 2007;313:3579-91 pubmed
    ..Finally, ablation of either periplakin or plectin, or both proteins simultaneously, impaired migration of MCF-7 epithelial sheets. Thus, we have identified a novel functional co-localisation between two plakin cytolinker proteins. ..
  8. Ruhrberg C, Hajibagheri M, Parry D, Watt F. Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. J Cell Biol. 1997;139:1835-49 pubmed
    ..We propose to name the 195-kD protein periplakin. ..
  9. Nishimori T, Tomonaga T, Matsushita K, Oh Ishi M, Kodera Y, Maeda T, et al. Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin. Proteomics. 2006;6:1011-8 pubmed
    ..These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression. ..

More Information


  1. Murdoch H, Feng G, Bächner D, Ormiston L, White J, Richter D, et al. Periplakin interferes with G protein activation by the melanin-concentrating hormone receptor-1 by binding to the proximal segment of the receptor C-terminal tail. J Biol Chem. 2005;280:8208-20 pubmed
    ..Periplakin is the first protein described to modify the capacity of the melanin-concentrating hormone-1 receptor to initiate signal transduction. ..
  2. Beekman J, Bakema J, van de Winkel J, Leusen J. Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity. Proc Natl Acad Sci U S A. 2004;101:10392-7 pubmed
    ..These data illustrate that intracellular protein interactions with a multisubunit FcR alpha-chain can confer unique properties to the receptor. ..
  3. Kazerounian S, Uitto J, Aho S. Unique role for the periplakin tail in intermediate filament association: specific binding to keratin 8 and vimentin. Exp Dermatol. 2002;11:428-38 pubmed
  4. Jefferson J, Ciatto C, Shapiro L, Liem R. Structural analysis of the plakin domain of bullous pemphigoid antigen1 (BPAG1) suggests that plakins are members of the spectrin superfamily. J Mol Biol. 2007;366:244-57 pubmed
    Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family of proteins. The plakins are multi-domain proteins that have been shown to interact with microtubules, actin filaments and intermediate filaments, as well as proteins ..
  5. Karashima T, Watt F. Interaction of periplakin and envoplakin with intermediate filaments. J Cell Sci. 2002;115:5027-37 pubmed
    ..has the shortest C-terminus of the plakin family, comprising only the linker domain found in all conventional plakins. By transient transfection of COS7 cells and primary human epidermal keratinocytes with deletion mutants of the ..
  6. Ward R, Jenkins L, Milligan G. Selectivity and functional consequences of interactions of family A G protein-coupled receptors with neurochondrin and periplakin. J Neurochem. 2009;109:182-92 pubmed publisher
    ..Details of the structure of the intracellular C-terminal tail of individual receptors will be required to fully understand the basis of such selectivity. ..
  7. Milligan G, Murdoch H, Kellett E, White J, Feng G. Interactions between G-protein-coupled receptors and periplakin: a selective means to regulate G-protein activation. Biochem Soc Trans. 2004;32:878-80 pubmed
    ..In each case, the site of interaction is within helix VIII of the receptor and periplakin limits agonist-mediated G-protein activation potentially by competing with G-protein for this region of the receptor. ..
  8. Sevilla L, Nachat R, Groot K, Klement J, Uitto J, Djian P, et al. Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier. J Cell Biol. 2007;179:1599-612 pubmed publisher
    ..Thus, combined loss of the cornified envelope proteins not only impairs the epidermal barrier, but also changes the composition of T cell subpopulations in the skin. ..
  9. Bottenberg W, Sanchez Soriano N, Alves Silva J, Hahn I, Mende M, Prokop A. Context-specific requirements of functional domains of the Spectraplakin Short stop in vivo. Mech Dev. 2009;126:489-502 pubmed publisher
    ..Taken together, our data clearly support the view that Spectraplakins function in tissue-specific modes in vivo, and even domains believed to be crucial for Spectraplakin function can be dispensable in specific contexts. ..
  10. Tonoike Y, Matsushita K, Tomonaga T, Katada K, Tanaka N, Shimada H, et al. Adhesion molecule periplakin is involved in cellular movement and attachment in pharyngeal squamous cancer cells. BMC Cell Biol. 2011;12:41 pubmed publisher
    ..PPL knockdown is related to reduced cellular movement and attachment activity in association with PI3K/Akt axis suppression, rather than malignant progression in pharyngeal cancer cells. ..
  11. Aho S, Rothenberger K, Tan E, Ryoo Y, Cho B, McLean W, et al. Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements. Genomics. 1999;56:160-8 pubmed
    ..These repetitive elements could lead to the clonal instability detected throughout the genomic P1 clones and may give rise to the genomic rearrangements possibly underlying the paraneoplastic pemphigus. ..
  12. Leung C, Green K, Liem R. Plakins: a family of versatile cytolinker proteins. Trends Cell Biol. 2002;12:37-45 pubmed
    ..b>Plakins are built from combinations of interacting domains that bind to microfilaments, microtubules, intermediate ..
  13. Sonnenberg A, Liem R. Plakins in development and disease. Exp Cell Res. 2007;313:2189-203 pubmed
    b>Plakins are large multi-domain molecules that have various functions to link cytoskeletal elements together and to connect them to junctional complexes...
  14. Long H, Boczonadi V, McInroy L, Goldberg M, Määttä A. Periplakin-dependent re-organisation of keratin cytoskeleton and loss of collective migration in keratin-8-downregulated epithelial sheets. J Cell Sci. 2006;119:5147-59 pubmed
    ..Thus, keratin 8 is required for the maintenance of epithelial integrity during migration and periplakin participates in the re-organisation of keratins in migrating cells...
  15. Osmanagic Myers S, Gregor M, Walko G, Burgstaller G, Reipert S, Wiche G. Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. J Cell Biol. 2006;174:557-68 pubmed
    ..These data establish a link between cytolinker-controlled cytoarchitecture/scaffolding functions of keratin IFs and specific MAP kinase cascades mediating distinct cellular responses. ..
  16. Boyer J, Bernstein M, Boudreau Larivière C. Plakins in striated muscle. Muscle Nerve. 2010;41:299-308 pubmed publisher
    ..Several studies suggest that plakins exert unique functions within various compartments of the muscle cell including the sarcolemma, the sarcomere, ..
  17. DiColandrea T, Karashima T, Maatta A, Watt F. Subcellular distribution of envoplakin and periplakin: insights into their role as precursors of the epidermal cornified envelope. J Cell Biol. 2000;151:573-86 pubmed
    Envoplakin and periplakin are two plakins that are precursors of the epidermal cornified envelope. We studied their distribution and interactions by transfection of primary human keratinocytes and other cells...
  18. Kalinin A, Kajava A, Steinert P. Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioessays. 2002;24:789-800 pubmed
    ..Here we describe our current understanding of CE structure, a possible mechanism of its assembly, and various disorders that cause a defective barrier. ..
  19. Pyle A, Li B, Maupin A, Guzman R, Crimmins D, Olson S, et al. Biomechanical stress induces novel arterial intima-enriched genes: implications for vascular adaptation to stress. Cardiovasc Pathol. 2010;19:e13-20 pubmed publisher
    ..We report the novel finding of a group of genes, previously studied in stratified epithelium, that were regulated by prolonged cyclic stress in vascular smooth muscle cells. This may have important implications to vascular disease. ..
  20. Aho S, Li K, Ryoo Y, McGee C, Ishida Yamamoto A, Uitto J, et al. Periplakin gene targeting reveals a constituent of the cornified cell envelope dispensable for normal mouse development. Mol Cell Biol. 2004;24:6410-8 pubmed
    ..Consequently, the primary role of periplakin may not relate to the physiology of the cornified cell envelope in epidermal keratinocytes but may reside in the challenges, which normal laboratory mice do not encounter. ..
  21. Aho S. Many faces of periplakin: domain-specific antibodies detect the protein throughout the epidermis, explaining the multiple protein-protein interactions. Cell Tissue Res. 2004;316:87-97 pubmed
    ..It is concluded that multiple localization and protein-protein interactions indicate a functional role for periplakin and its domains throughout the epithelial differentiation. ..
  22. Muzio M, Scielzo C, Frenquelli M, Bachi A, De Palma M, Alessio M, et al. HS1 complexes with cytoskeleton adapters in normal and malignant chronic lymphocytic leukemia B cells. Leukemia. 2007;21:2067-70 pubmed
  23. Gupta T, Marlow F, Ferriola D, Mackiewicz K, Dapprich J, Monos D, et al. Microtubule actin crosslinking factor 1 regulates the Balbiani body and animal-vegetal polarity of the zebrafish oocyte. PLoS Genet. 2010;6:e1001073 pubmed publisher
    ..These data provide the first evidence for a role for spectraplakins in polarization of the vertebrate oocyte and egg. ..
  24. Wang Y, Chen W, Huang Z, Yang Z, Zhang B, Wang J, et al. Expression of the membrane-cytoskeletal linker Ezrin in salivary gland adenoid cystic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:96-104 pubmed publisher
    ..The increased expression of Ezrin and its partners, CD44v6, iNOS, and Ki-67, in SACC correlated with histologic patterns, may play a role in distant metastasis, and might indicate poor clinical outcome. ..
  25. Brooke M, Nitoiu D, Kelsell D. Cell-cell connectivity: desmosomes and disease. J Pathol. 2012;226:158-71 pubmed publisher
    ..We will examine the various pathologies that result from impairment of desmosome function and thereby demonstrate the importance of desmosomes to tissues and to the organism as a whole. ..
  26. Boczonadi V, Määttä A. Functional Analysis of Periplakin and Envoplakin, Cytoskeletal Linkers, and Cornified Envelope Precursor Proteins. Methods Enzymol. 2016;569:309-29 pubmed publisher
    ..These two plakins have a structural role in the assembly of the cornified envelope (CE), the terminal stage of epidermal ..
  27. Seow C, Solway J. Mechanical and structural plasticity. Compr Physiol. 2011;1:283-93 pubmed publisher
  28. Künzli K, Favre B, Chofflon M, Borradori L. One gene but different proteins and diseases: the complexity of dystonin and bullous pemphigoid antigen 1. Exp Dermatol. 2016;25:10-6 pubmed publisher
    ..In this review, we summarize recent advances of our knowledge about several BPAG1 isoforms, their role in various biological processes and in human diseases. ..
  29. Mouquet H, Drouot L, Charlionnet R, Arnoult C, Bonnet Bayeux F, Thomas M, et al. Proteomic analysis of the autoantibody response following immunization with a single autoantigen. Proteomics. 2006;6:4829-37 pubmed
  30. Kempe S, Kestler H, Lasar A, Wirth T. NF-kappaB controls the global pro-inflammatory response in endothelial cells: evidence for the regulation of a pro-atherogenic program. Nucleic Acids Res. 2005;33:5308-19 pubmed
    ..We conclude that targeting the IKK/NF-kappaB pathway or specific genes downstream may be effective for the control or prevention of chronic inflammatory diseases such as atherosclerosis. ..
  31. Takaki S. [Sh2b3/Lnk family adaptor proteins in the regulation of lymphohematopoiesis]. Nihon Rinsho Meneki Gakkai Kaishi. 2008;31:440-7 pubmed
    ..This review summarizes roles of Sh2b3/Lnk in the regulation of B-lymphopoiesis and HSCs expansion and function, and briefly introduces our approach for modulating HSCs function by targeting Sh2b3/Lnk-mediated pathways. ..
  32. Choi Y, Woo S, Cho S, Moon H, Yun Y, Kim J, et al. Brain-metastatic triple-negative breast cancer cells regain growth ability by altering gene expression patterns. Cancer Genomics Proteomics. 2013;10:265-75 pubmed
    ..Gene expression patterns in TNBC and BrM reflect cancer cell growth in regions of metastasis. ..
  33. Roca Cusachs P, Iskratsch T, Sheetz M. Finding the weakest link: exploring integrin-mediated mechanical molecular pathways. J Cell Sci. 2012;125:3025-38 pubmed publisher
    ..All these define mechanical molecular pathways in cells, which are emerging as key regulators of cell function alongside better studied biochemical pathways...
  34. Wang J, Bu D, Li T, Zheng R, Zhang B, Chen X, et al. Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigus. Br J Dermatol. 2005;153:558-64 pubmed
  35. Rivera J. Adaptors discriminate mast-cell cytokine production from eicosanoid production and degranulation. Trends Immunol. 2006;27:251-3 pubmed
    ..The new findings place this complex at the forefront in discriminating between signals required for cytokine production and those required for mast-cell degranulation and eicosanoid production. ..
  36. Suzuki A, Horiuchi A, Ashida T, Miyamoto T, Kashima H, Nikaido T, et al. Cyclin A2 confers cisplatin resistance to endometrial carcinoma cells via up-regulation of an Akt-binding protein, periplakin. J Cell Mol Med. 2010;14:2305-17 pubmed publisher
    ..These results indicate cyclin A2 to be involved in the acquisition of aggressive behaviour of tumour cells through the activation of PI3K by cyclin A2-induced periplakin, and to be a promising therapeutic target. ..
  37. Waschke J. The desmosome and pemphigus. Histochem Cell Biol. 2008;130:21-54 pubmed publisher
    ..To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required. ..
  38. Pines M, Housden B, Bernard F, Bray S, Röper K. The cytolinker Pigs is a direct target and a negative regulator of Notch signalling. Development. 2010;137:913-22 pubmed publisher
  39. Zahreddine H, Zhang H, Diogon M, Nagamatsu Y, Labouesse M. CRT-1/calreticulin and the E3 ligase EEL-1/HUWE1 control hemidesmosome maturation in C. elegans development. Curr Biol. 2010;20:322-7 pubmed publisher
    Hemidesmosomes connect the extracellular matrix (ECM) to intermediate filaments through ECM receptors and plakins (plectin and BPAG1e). They affect tissue integrity, wound healing, and carcinoma invasion...
  40. Taillé C, Grootenboer Mignot S, Boursier C, Michel L, Debray M, Fagart J, et al. Identification of periplakin as a new target for autoreactivity in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183:759-66 pubmed publisher
    ..Patients with IPF with anti-PPL Abs had a more severe respiratory disease, despite no difference in survival. We found a new circulating autoAb directed against PPL in patients with IPF, associated with a more severe disease. ..
  41. Mimouni D, Anhalt G, Lazarova Z, Aho S, Kazerounian S, Kouba D, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147:725-32 pubmed
    ..Serum autoantibodies against plakin proteins were the most constant diagnostic markers. Pulmonary injury appears to account for the very high mortality rates observed. ..
  42. Karlhofer F, Hashimoto T, Slupetzky K, Kiss M, Liu Y, Amagai M, et al. 230-kDa and 190-kDa proteins in addition to desmoglein 1 as immunological targets in a subset of pemphigus foliaceus with a combined cell-surface and basement membrane zone immune staining pattern. Exp Dermatol. 2003;12:646-54 pubmed
    ..Further studies will be required to substantiate the frequency of this occurrence and to unravel its pathogenic significance. ..
  43. Schaefer A, Nethe M, Hordijk P. Ubiquitin links to cytoskeletal dynamics, cell adhesion and migration. Biochem J. 2012;442:13-25 pubmed publisher
    ..Since ubiquitylation is fast as well as reversible, it represents a bona fide signalling event, which is used to fine-tune a cell's responses to receptor agonists. ..
  44. Huang Y, Li J, Zhu X. Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in patients with paraneoplastic pemphigus. Arch Dermatol Res. 2009;301:703-9 pubmed publisher
    ..Our findings indicate that ELISAs using the recombinant proteins containing linker subdomains of envoplakin and periplakin expressed in a human cell line as the antigens are highly sensitive and specific for the diagnosis of PNP. ..
  45. Bouameur J, Favre B, Borradori L. Plakins, a versatile family of cytolinkers: roles in skin integrity and in human diseases. J Invest Dermatol. 2014;134:885-894 pubmed publisher
    ..Inherited and acquired defects of plakins in humans and in animal models potentially lead to dramatic manifestations in the skin, striated muscles, and/or ..
  46. Beekman J, Bakema J, van der Linden J, Tops B, Hinten M, van Vugt M, et al. Modulation of FcgammaRI (CD64) ligand binding by blocking peptides of periplakin. J Biol Chem. 2004;279:33875-81 pubmed
    ..These data support a dominant-negative role of C-terminal periplakin for FcgammaRI biological activity and implicate periplakin as a novel regulator of FcgammaRI in immune cells. ..
  47. Watt H, Kharmate G, Kumar U. Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cells. Cell Signal. 2009;21:428-39 pubmed publisher
    ..To the best of our knowledge, this is the first report describing crosstalk/interactions between SSTRs and ErbBs. ..
  48. Escobar Aguirre M, Zhang H, Jamieson Lucy A, Mullins M. Microtubule-actin crosslinking factor 1 (Macf1) domain function in Balbiani body dissociation and nuclear positioning. PLoS Genet. 2017;13:e1006983 pubmed publisher
    ..To our knowledge, this is also the first study to use genome editing to unravel the module-dependent function of a cytoskeletal linker. ..
  49. Al Jassar C, Bernadό P, Chidgey M, Overduin M. Hinged plakin domains provide specialized degrees of articulation in envoplakin, periplakin and desmoplakin. PLoS ONE. 2013;8:e69767 pubmed publisher
  50. Valencia R, Walko G, Janda L, Novacek J, Mihailovska E, Reipert S, et al. Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes. Mol Biol Cell. 2013;24:768-84 pubmed publisher
    ..Our results open new perspectives on cytolinker-coordinated IF-MT interaction and its physiological significance...
  51. Aho S. Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases. Exp Dermatol. 2004;13:700-7 pubmed
    ..The involvement of multiple caspases in the destruction of epithelial cell integrity ensures the efficient elimination of cytoskeleton, but also provides specificity for selectively targeting individual adhesion molecules. ..
  52. Lin C, Chen H, Leung C, Parry D, Liem R. Microtubule actin crosslinking factor 1b: a novel plakin that localizes to the Golgi complex. J Cell Sci. 2005;118:3727-38 pubmed
    ..Reducing the level of MACF1 proteins by small-interfering RNA resulted in the dispersal of the Golgi complex. ..
  53. Buttermore E, Dupree J, Cheng J, An X, Tessarollo L, Bhat M. The cytoskeletal adaptor protein band 4.1B is required for the maintenance of paranodal axoglial septate junctions in myelinated axons. J Neurosci. 2011;31:8013-24 pubmed publisher
    ..1B plays a pivotal role in interactions between the paranodal AGSJs and axonal cytoskeleton, and that 4.1B is critically required for long-term maintenance of axonal domains in myelinated axons. ..