Desmosome regulation and signaling in disease

Cell and Tissue Research

Volumn 360, Issue 3, 2015, Pages 501-512

  Broussard, Joshua A ^a   Getsios, Spiro ^a   Green, Kathleen J ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Desmoplakin; Desmosomal cadherins; Desmosome; Plakoglobin; Plakophilin

Indexed keywords

BETA CATENIN; CADHERIN; CONNEXIN 43; DESMOCOLLIN; DESMOCOLLIN 1; DESMOCOLLIN 2; DESMOCOLLIN 3; DESMOGLEIN; DESMOGLEIN 1; DESMOGLEIN 1 ANTIBODY; DESMOGLEIN 2; DESMOGLEIN 3; DESMOGLEIN 3 ANTIBODY; DESMOGLEIN 4; DESMOPLAKIN; EPHRIN A2; EPIDERMAL GROWTH FACTOR RECEPTOR; INTERMEDIATE FILAMENT PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; NUCLEOPHOSMIN; PLAKOGLOBIN; PLAKOPHILIN; PROTEIN KINASE C ALPHA; PROTEIN P53; RAS PROTEIN; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE 2; STRATIFIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; UVOMORULIN; PROTEIN;

ALLERGY; ARRHYTHMOGENESIS; BREAST CANCER; BRUGADA SYNDROME; CARCINOGENESIS; CELL ADHESION; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL MEMBRANE; DERMATITIS; DESMOSOME; DIGESTIVE SYSTEM CANCER; DISEASE SEVERITY; HEART RIGHT VENTRICLE DYSPLASIA; HOMOZYGOSITY; HUMAN; INTERMEDIATE FILAMENT; INTERNALIZATION; KERATINOCYTE; MISSENSE MUTATION; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; NONISCHEMIC CARDIOMYOPATHY; NONSENSE MUTATION; PANCREAS CANCER; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOMA; SKIN DERMATITIS MULTIPLE ALLERGY AND METABOLIC WASTING SYNDROME; ANIMAL; DISEASES; METABOLISM;

ANIMALS; DESMOSOMES; DISEASE; HUMANS; PROTEINS; SIGNAL TRANSDUCTION;

EID: 84930278391     PISSN: 0302766X     EISSN: 14320878     Source Type: Journal    
DOI: 10.1007/s00441-015-2136-5     Document Type: Review

References (112)

1. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda T, Ramaswamy S, Ting DT, Lin CP, Toner M, Haber DA, Maheswaran S (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158:1110–1122
2. Aktary Z, Pasdar M (2012) Plakoglobin: role in tumorigenesis and metastasis. Int J Cell Biol 2012:189521
3. Aktary Z, Pasdar M (2013) Plakoglobin represses SATB1 expression and decreases in vitro proliferation, migration and invasion. PLoS One 8:e78388
4. Aktary Z, Chapman K, Lam L, Lo A, Ji C, Graham K, Cook L, Li L, Mackey JR, Pasdar M (2010) Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1. Oncogene 29:2118–2129
5. Aktary Z, Kulak S, Mackey J, Jahroudi N, Pasdar M (2013) Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3sigma. J Cell Sci 126:3031–3042
6. Amagai M, Stanley JR (2012) Desmoglein as a target in skin disease and beyond. J Invest Dermatol 132:776–784
7. Arimoto K, Burkart C, Yan M, Ran D, Weng S, Zhang DE (2014) Plakophilin-2 promotes tumor development by enhancing ligand-dependent and -independent epidermal growth factor receptor dimerization and activation. Mol Cell Biol 34:3843–3854
8. Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ (2007) A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 81:964–973
9. Asimaki A, Syrris P, Ward D, Guereta LG, Saffitz JE, McKenna WJ (2009) Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy related to novel desmoplakin mutations. J Cutan Pathol 36:553–559
10. Bass-Zubek AE, Hobbs RP, Amargo EV, Garcia NJ, Hsieh SN, Chen X, Wahl JK 3rd, Denning MF, Green KJ (2008) Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly. J Cell Biol 181:605–613
11. Bass-Zubek AE, Godsel LM, Delmar M, Green KJ (2009) Plakophilins: multifunctional scaffolds for adhesion and signaling. Curr Opin Cell Biol 21:708–716
12. Beyer I, van Rensburg R, Strauss R, Li Z, Wang H, Persson J, Yumul R, Feng Q, Song H, Bartek J, Fender P, Lieber A (2011) Epithelial junction opener JO-1 improves monoclonal antibody therapy of cancer. Cancer Res 71:7080–7090
13. Beyer I, Cao H, Persson J, Song H, Richter M, Feng Q, Yumul R, van Rensburg R, Li Z, Berenson R, Carter D, Roffler S, Drescher C, Lieber A (2012) Coadministration of epithelial junction opener JO-1 improves the efficacy and safety of chemotherapeutic drugs. Clin Cancer Res 18:3340–3351
14. Bierkamp C, McLaughlin KJ, Schwarz H, Huber O, Kemler R (1996) Embryonic heart and skin defects in mice lacking plakoglobin. Dev Biol 180:780–785
15. Brennan D, Mahoney MG (2009) Increased expression of Dsg2 in malignant skin carcinomas: a tissue-microarray based study. Cell Adh Migr 3:148–154
16. Breuninger S, Reidenbach S, Sauer CG, Ströbel P, Pfitzenmaier J, Trojan L, Hofmann I (2010) Desmosomal plakophilins in the prostate and prostatic adenocarcinomas: implications for diagnosis and tumor progression. Am J Pathol 176:2509–2519
17. Brooke MA, Nitoiu D, Kelsell DP (2012) Cell-cell connectivity: desmosomes and disease. J Pathol 226:158–171
18. Cabral RM, Liu L, Hogan C, Dopping-Hepenstal PJ, Winik BC, Asial RA, Dobson R, Mein CA, Baselaga PA, Mellerio JE, Nanda A, Boente Mdel C, Kelsell DP, McGrath JA, South AP (2010) Homozygous mutations in the 5′ region of the JUP gene result in cutaneous disease but normal heart development in children. J Invest Dermatol 130:1543–1550
19. Cabral RM, Tattersall D, Patel V, McPhail GD, Hatzimasoura E, Abrams DJ, South AP, Kelsell DP (2012) The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes. J Cell Sci 125:2853–2861
20. Campuzano O, Alcalde M, Berne P, Zorio E, Iglesias A, Navarro-Manchón J, Brugada J, Brugada R (2013) Role of novel DSP_p.Q986X genetic variation in arrhythmogenic right ventricular cardiomyopathy. Eur J Med Genet 56:541–545
21. Cerrone M, Lin X, Zhang M, Agullo-Pascual E, Pfenniger A, Chkourko Gusky H, Novelli V, Kim C, Tirasawadichai T, Judge DP, Rothenberg E, Chen HS, Napolitano C, Priori SG, Delmar M (2014) Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype. Circulation 129:1092–1103
22. Chalabreysse L, Senni F, Bruyère P, Aime B, Ollagnier C, Bozio A, Bouvagnet P (2011) A new hypo/oligodontia syndrome: Carvajal/Naxos syndrome secondary to desmoplakin-dominant mutations. J Dent Res 90:58–64
23. Chen YJ, Chang JT, Lee L, Wang HM, Liao CT, Chiu CC, Chen PJ, Cheng AJ (2007) DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. Oncogene 26:467–476
24. Chen J, Nekrasova OE, Patel DM, Klessner JL, Godsel LM, Koetsier JL, Amargo EV, Desai BV, Green KJ (2012) The C-terminal unique region of desmoglein 2 inhibits its internalization via tail-tail interactions. J Cell Biol 199:699–711
25. Chen YJ, Lee LY, Chao YK, Chang JT, Lu YC, Li HF, Chiu CC, Li YC, Li YL, Chiou JF, Cheng AJ (2013) DSG3 facilitates cancer cell growth and invasion through the DSG3-plakoglobin-TCF/LEF-Myc/cyclin D1/MMP signaling pathway. PLoS One 8:e64088
26. Chen SN, Gurha P, Lombardi R, Ruggiero A, Willerson JT, Marian AJ (2014) The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy. Circ Res 114:454–468
27. Chidgey M, Dawson C (2007) Desmosomes: a role in cancer? Br J Cancer 96:1783–1787
28. Chkourko HS, Guerrero-Serna G, Lin X, Darwish N, Pohlmann JR, Cook KE, Martens JR, Rothenberg E, Musa H, Delmar M (2012) Remodeling of mechanical junctions and of microtubule-associated proteins accompany cardiac connexin43 lateralization. Heart Rhythm 9:1133–1140
29. Chun MG, Hanahan D (2010) Genetic deletion of the desmosomal component desmoplakin promotes tumor microinvasion in a mouse model of pancreatic neuroendocrine carcinogenesis. PLoS Genet 6:e1001120
30. Cirillo N, AlShwaimi E, McCullough M, Prime SS (2014) Pemphigus vulgaris autoimmune globulin induces Src-dependent tyrosine-phosphorylation of plakophilin 3 and its detachment from desmoglein 3. Autoimmunity 47:134–140
31. Demirag GG, Sullu Y, Yucel I (2012) Expression of Plakophilins (PKP1, PKP2, and PKP3) in breast cancers. Med Oncol 29:1518–1522
32. Dubash AD, Koetsier JL, Amargo EV, Najor NA, Harmon RM, Green KJ (2013) The GEF Bcr activates RhoA/MAL signaling to promote keratinocyte differentiation via desmoglein-1. J Cell Biol 202:653–666
33. Dusek RL, Attardi LD (2011) Desmosomes: new perpetrators in tumour suppression. Nat Rev Cancer 11:317–323
34. Fang WK, Liao LD, Li LY, Xie YM, Xu XE, Zhao WJ, Wu JY, Zhu MX, Wu ZY, Du ZP, Wu BL, Xie D, Guo MZ, Xu LY, Li EM (2013) Down-regulated desmocollin-2 promotes cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling in oesophageal squamous cell carcinoma. J Pathol 231:257–270
35. Fang WK, Liao LD, Gu W, Chen B, Wu ZY, Wu JY, Shen J, Xu LY, Li EM (2014) Down-regulated gamma-catenin expression is associated with tumor aggressiveness in esophageal cancer. World J Gastroenterol 20:5839–5848
36. Fidler LM, Wilson GJ, Liu F, Cui X, Scherer SW, Taylor GP, Hamilton RM (2009) Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations. J Cell Mol Med 13:4219–4228
37. Franzen CA, Todorović V, Desai BV, Mirzoeva S, Yang XJ, Green KJ, Pelling JC (2012) The desmosomal armadillo protein plakoglobin regulates prostate cancer cell adhesion and motility through vitronectin-dependent Src signaling. PLoS One 7:e42132
38. Furukawa C, Daigo Y, Ishikawa N, Kato T, Ito T, Tsuchiya E, Sone S, Nakamura Y (2005) Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Cancer Res 65:7102–7110
39. Gallicano GI, Kouklis P, Bauer C, Yin M, Vasioukhin V, Degenstein L, Fuchs E (1998) Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J Cell Biol 143:2009–2022
40. Garrod D, Chidgey M (2008) Desmosome structure, composition and function. Biochim Biophys Acta 1778:572–587
41. Gehmlich K, Asimaki A, Cahill TJ, Ehler E, Syrris P, Zachara E, Re F, Avella A, Monserrat L, Saffitz JE, McKenna WJ (2010) Novel missense mutations in exon 15 of desmoglein-2: role of the intracellular cadherin segment in arrhythmogenic right ventricular cardiomyopathy? Heart Rhythm 7:1446–1453
42. Gehmlich K, Syrris P, Reimann M, Asimaki A, Ehler E, Evans A, Quarta G, Pantazis A, Saffitz JE, McKenna WJ (2012) Molecular changes in the heart of a severe case of arrhythmogenic right ventricular cardiomyopathy caused by a desmoglein-2 null allele. Cardiovasc Pathol 21:275–282
43. Getsios S, Simpson CL, Kojima S, Harmon R, Sheu LJ, Dusek RL, Cornwell M, Green KJ (2009) Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. J Cell Biol 185:1243–1258
44. Godsel LM, Hsieh SN, Amargo EV, Bass AE, Pascoe-McGillicuddy LT, Huen AC, Thorne ME, Gaudry CA, Park JK, Myung K, Goldman RD, Chew TL, Green KJ (2005) Desmoplakin assembly dynamics in four dimensions: multiple phases differentially regulated by intermediate filaments and actin. J Cell Biol 171:1045–1059
45. Godsel LM, Dubash AD, Bass-Zubek AE, Amargo EV, Klessner JL, Hobbs RP, Chen X, Green KJ (2010) Plakophilin 2 couples actomyosin remodeling to desmosomal plaque assembly via RhoA. Mol Biol Cell 21:2844–2859
46. Gomes J, Finlay M, Ahmed AK, Ciaccio EJ, Asimaki A, Saffitz JE, Quarta G, Nobles M, Syrris P, Chaubey S, McKenna WJ, Tinker A, Lambiase PD (2012) Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study. Eur Heart J 33:1942–1953
47. Green KJ, Simpson CL (2007) Desmosomes: new perspectives on a classic. J Invest Dermatol 127:2499–2515
48. Harmon RM, Simpson CL, Johnson JL, Koetsier JL, Dubash AD, Najor NA, Sarig O, Sprecher E, Green KJ (2013) Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation. J Clin Invest 123:1556–1570
49. Harris AR, Daeden A, Charras GT (2014) Formation of adherens junctions leads to the emergence of a tissue-level tension in epithelial monolayers. J Cell Sci 127:2507–2517
50. Has C, Jakob T, He Y, Kiritsi D, Hausser I, Bruckner-Tuderman L (2015) Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies. Br J Dermatol 172:257–261
51. Hatzfeld M (2007) Plakophilins: multifunctional proteins or just regulators of desmosomal adhesion? Biochim Biophys Acta 1773:69–77
52. Hobbs RP, Green KJ (2012) Desmoplakin regulates desmosome hyperadhesion. J Invest Dermatol 132:482–485
53. Hobbs RP, Han SY, van der Zwaag PA, Bolling MC, Jongbloed JD, Jonkman MF, Getsios S, Paller AS, Green KJ (2010) Insights from a desmoplakin mutation identified in lethal acantholytic epidermolysis bullosa. J Invest Dermatol 130:2680–2683
54. Hobbs RP, Amargo EV, Somasundaram A, Simpson CL, Prakriya M, Denning MF, Green KJ (2011) The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling. FASEB J 25:990–1001
55. Johnson JL, Najor NA, Green KJ (2014) Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease. Cold Spring Harb Perspect Med 4:a015297
56. Jolly PS, Berkowitz P, Bektas M, Lee HE, Chua M, Diaz LA, Rubenstein DS (2010) p38MAPK signaling and desmoglein-3 internalization are linked events in pemphigus acantholysis. J Biol Chem 285:8936–8941
57. Kamekura R, Kolegraff KN, Nava P, Hilgarth RS, Feng M, Parkos CA, Nusrat A (2014) Loss of the desmosomal cadherin desmoglein-2 suppresses colon cancer cell proliferation through EGFR signaling. Oncogene 33:4531–4536
58. Kapplinger JD, Landstrom AP, Salisbury BA, Callis TE, Pollevick GD, Tester DJ, Cox MG, Bhuiyan Z, Bikker H, Wiesfeld AC, Hauer RN, van Tintelen JP, Jongbloed JD, Calkins H, Judge DP, Wilde AA, Ackerman MJ (2011) Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 57:2317–2327
59. Keller DI, Stepowski D, Balmer C, Simon F, Guenthard J, Bauer F, Itin P, David N, Drouin-Garraud V, Fressart V (2012) De novo heterozygous desmoplakin mutations leading to Naxos-Carvajal disease. Swiss Med Wkly 142:w13670
60. Khapare N, Kundu ST, Sehgal L, Sawant M, Priya R, Gosavi P, Gupta N, Alam H, Karkhanis M, Naik N, Vaidya MM, Dalal SN (2012) Plakophilin3 loss leads to an increase in PRL3 levels promoting K8 dephosphorylation, which is required for transformation and metastasis. PLoS One 7:e38561
61. Kim W, Kim M, Jho EH (2013) Wnt/beta-catenin signalling: from plasma membrane to nucleus. Biochem J 450:9–21
62. Kirchner F, Schuetz A, Boldt LH, Martens K, Dittmar G, Haverkamp W, Thierfelder L, Heinemann U, Gerull B (2012) Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations. Circ Cardiovasc Genet 5:400–411
63. Kitajima Y (2013) New insights into desmosome regulation and pemphigus blistering as a desmosome-remodeling disease. Kaohsiung J Med Sci 29:1–13
64. Koetsier JL, Amargo EV, Todorović V, Green KJ, Godsel LM (2014) Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and integrin protein expression. J Invest Dermatol 134:112–122
65. Kolegraff K, Nava P, Helms MN, Parkos CA, Nusrat A (2011) Loss of desmocollin-2 confers a tumorigenic phenotype to colonic epithelial cells through activation of Akt/beta-catenin signaling. Mol Biol Cell 22:1121–1134
66. Kowalczyk AP, Green KJ (2013) Structure, function, and regulation of desmosomes. Prog Mol Biol Transl Sci 116:95–118
67. Kurzen H, Munzing I, Hartschuh W (2003) Expression of desmosomal proteins in squamous cell carcinomas of the skin. J Cutan Pathol 30:621–630
68. Lai-Cheong JE, Arita K, McGrath JA (2007) Genetic diseases of junctions. J Invest Dermatol 127:2713–2725
69. Lam L, Aktary Z, Bishay M, Werkman C, Kuo CY, Heacock M, Srivastava N, Mackey JR, Pasdar M (2012) Regulation of subcellular distribution and oncogenic potential of nucleophosmin by plakoglobin. Oncogenesis 1:e4
70. Li D, Liu Y, Maruyama M, Zhu W, Chen H, Zhang W, Reuter S, Lin SF, Haneline LS, Field LJ, Chen PS, Shou W (2011a) Restrictive loss of plakoglobin in cardiomyocytes leads to arrhythmogenic cardiomyopathy. Hum Mol Genet 20:4582–4596
71. Li J, Swope D, Raess N, Cheng L, Muller EJ, Radice GL (2011b) Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling. Mol Cell Biol 31:1134–1144
72. Li D, Zhang W, Liu Y, Haneline LS, Shou W (2012) Lack of plakoglobin in epidermis leads to keratoderma. J Biol Chem 287:10435–10443
73. Lin S, Gordon K, Kaplan N, Getsios S (2010) Ligand targeting of EphA2 enhances keratinocyte adhesion and differentiation via desmoglein 1. Mol Biol Cell 21:3902–3914
74. Lombardi R, da Graca Cabreira-Hansen M, Bell A, Fromm RR, Willerson JT, Marian AJ (2011) Nuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy. Circ Res 109:1342–1353
75. Lopez-Ayala JM, Gomez-Milanes I, Sánchez Muñoz JJ, Ruiz-Espejo F, Ortíz M, González-Carrillo J, López-Cuenca D, Oliva-Sandoval MJ, Monserrat L, Valdés M, Gimeno JR (2014) Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype. Europace 16:1838–1846
76. McGrath JA, McMillan JR, Shemanko CS, Runswick SK, Leigh IM, Lane EB, Garrod DR, Eady RA (1997) Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet 17:240–244
77. McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, Norman M, Baboonian C, Jeffery S, McKenna WJ (2000) Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355:2119–2124
78. Morgan RG, Pearn L, Liddiard K, Pumford SL, Burnett AK, Tonks A, Darley RL (2013) Gamma-catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of betacatenin. Leukemia 27:336–343
79. Muller T, Bain G, Wang X, Papkoff J (2002) Regulation of epithelial cell migration and tumor formation by beta-catenin signaling. Exp Cell Res 280:119–133
80. Niessen CM, Gottardi CJ (2008) Molecular components of the adherens junction. Biochim Biophys Acta 1778:562–571
81. Patel DM, Dubash AD, Kreitzer G, Green KJ (2014) Disease mutations in desmoplakin inhibit Cx43 membrane targeting mediated by desmoplakin-EB1 interactions. J Cell Biol 206:779–797
82. Pigors M, Kiritsi D, Krümpelmann S, Wagner N, He Y, Podda M, Kohlhase J, Hausser I, Bruckner-Tuderman L, Has C (2011) Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: a novel clinico-genetic entity. Hum Mol Genet 20:1811–1819
83. Rasmussen TB, Nissen PH, Palmfeldt J, Gehmlich K, Dalager S, Jensen UB, Kim WY, Heickendorff L, Mølgaard H, Jensen HK, Baandrup UT, Bross P, Mogensen J (2014) Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis. Circ Cardiovasc Genet 7:230–240
84. Saito M, Stahley SN, Caughman CY, Mao X, Tucker DK, Payne AS, Amagai M, Kowalczyk AP (2012) Signaling dependent and independent mechanisms in pemphigus vulgaris blister formation. PLoS One 7:e50696
85. Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A, Isakov O, Koetsier JL, Gat A, Goldberg I, Bergman R, Spiegel R, Eytan O, Geller S, Peleg S, Shomron N, Goh CS, Wilson NJ, Smith FJ, Pohler E, Simpson MA, McLean WH, Irvine AD, Horowitz M, McGrath JA, Green KJ, Sprecher E (2013) Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet 45:1244–1248
86. Sato PY, Coombs W, Lin X, Nekrasova O, Green KJ, Isom LL, Taffet SM, Delmar M (2011) Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res 109:193–201
87. Scott CA, Tattersall D, O’Toole EA, Kelsell DP (2012) Connexins in epidermal homeostasis and skin disease. Biochim Biophys Acta 1818:1952–1961
88. Shaw RM (2014) Desmosomal hotspots, microtubule delivery, and cardiac arrhythmogenesis. Dev Cell 31:139–140
89. Shaw RM, Fay AJ, Puthenveedu MA, von Zastrow M, Jan YN, Jan LY (2007) Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions. Cell 128:547–560
90. Shirakata Y, Amagai M, Hanakawa Y, Nishikawa T, Hashimoto K (1998) Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1. J Invest Dermatol 110:76–78
91. Sklyarova T, Bonne S, D’Hooge P, Denecker G, Goossens S, De Rycke R, Borgonie G, Bösl M, van Roy F, van Hengel J (2008) Plakophilin-3-deficient mice develop hair coat abnormalities and are prone to cutaneous inflammation. J Invest Dermatol 128:1375–1385
92. Spindler V, Dehner C, Hübner S, Waschke J (2014) Plakoglobin but not desmoplakin regulates keratinocyte cohesion via modulation of p38MAPK signaling. J Invest Dermatol 134:1655–1664
93. Swope D, Cheng L, Gao E, Li J, Radice GL (2012) Loss of cadherin-binding proteins beta-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis. Mol Cell Biol 32:1056–1067
94. Tanaka A, Lai-Cheong JE, Café ME, Gontijo B, Salomão PR, Pereira L, McGrath JA (2009) Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families. Br J Dermatol 160:692–697
95. Thomason HA, Scothern A, McHarg S, Garrod DR (2010) Desmosomes: adhesive strength and signalling in health and disease. Biochem J 429:419–433
96. Todorović V, Desai BV, Patterson MJ, Amargo EV, Dubash AD, Yin T, Jones JC, Green KJ (2010) Plakoglobin regulates cell motility through Rho- and fibronectin-dependent Src signaling. J Cell Sci 123:3576–3586
97. Todorović V, Koetsier JL, Godsel LM, Green KJ (2014) Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation. Mol Biol Cell 25:3749–3764
98. Tsang SM, Liu L, Teh MT, Wheeler A, Grose R, Hart IR, Garrod DR, Fortune F, Wan H (2010) Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src. PLoS One 5:e14211
99. Tsang SM, Brown L, Lin K, Liu L, Piper K, O’Toole EA, Grose R, Hart IR, Garrod DR, Fortune F, Wan H (2012) Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris. J Pathol 227:81–93
100. Tucker DK, Stahley SN, Kowalczyk AP (2014) Plakophilin-1 protects keratinocytes from pemphigus vulgaris IgG by forming calcium-independent desmosomes. J Invest Dermatol 134:1033–1043
101. Valladares-Ayerbes M, Diaz-Prado S, Reboredo M, Medina V, Lorenzo-Patiño MJ, Iglesias-Díaz P, Haz M, Pértega S, Santamarina I, Blanco M, Quindós-Varela M, Figueroa A, Antón-Aparicio LM (2010) Evaluation of plakophilin-3 mRNA as a biomarker for detection of circulating tumor cells in gastrointestinal cancer patients. Cancer Epidemiol Biomarkers Prev 19:1432–1440
102. van der Velden HM, Jongsma HJ (2002) Cardiac gap junctions and connexins: their role in atrial fibrillation and potential as therapeutic targets. Cardiovasc Res 54:270–279
103. van der Wier G, Pas HH, Kramer D, Diercks GF, Jonkman MF (2014) Smaller desmosomes are seen in the skin of pemphigus patients with anti-desmoglein 1 antibodies but not in patients with anti-desmoglein 3 antibodies. J Invest Dermatol 134:2287–2290
104. Vasioukhin V, Bowers E, Bauer C, Degenstein L, Fuchs E (2001) Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol 3:1076–1085
105. Wang H, Li Z, Yumul R, Lara S, Hemminki A, Fender P, Lieber A (2011a) Multimerization of adenovirus serotype 3 fiber knob domains is required for efficient binding of virus to desmoglein 2 and subsequent opening of epithelial junctions. J Virol 85:6390–6402
106. Wang H, Li ZY, Liu Y, Persson J, Beyer I, Möller T, Koyuncu D, Drescher MR, Strauss R, Zhang XB, Wahl JK 3rd, Urban N, Drescher C, Hemminki A, Fender P, Lieber A (2011b) Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med 17:96–104
107. Wang H, Yumul R, Cao H, Ran L, Fan X, Richter M, Epstein F, Gralow J, Zubieta C, Fender P, Lieber A (2013) Structural and functional studies on the interaction of adenovirus fiber knobs and desmoglein 2. J Virol 87:11346–11362
108. Wolf A, Krause-Gruszczynska M, Birkenmeier O, Ostareck-Lederer A, Hüttelmaier S, Hatzfeld M (2010) Plakophilin 1 stimulates translation by promoting eIF4A1 activity. J Cell Biol 188:463–471
109. Wolf A, Rietscher K, Glaß M, Hüttelmaier S, Schutkowski M, Ihling C, Sinz A, Wingenfeld A, Mun A, Hatzfeld M (2013) Insulin signaling via Akt2 switches plakophilin 1 function from stabilizing cell adhesion to promoting cell proliferation. J Cell Sci 126:1832–1844
110. Yang Z, Bowles NE, Scherer SE, Taylor MD, Kearney DL, Ge S, Nadvoretskiy VV, DeFreitas G, Carabello B, Brandon LI, Godsel LM, Green KJ, Saffitz JE, Li H, Danieli GA, Calkins H, Marcus F, Towbin JA (2006) Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Res 99:646–655
111. Yang L, Chen Y, Cui T, Knösel T, Zhang Q, Albring KF, Huber O, Petersen I (2012) Desmoplakin acts as a tumor suppressor by inhibition of the Wnt/beta-catenin signaling pathway in human lung cancer. Carcinogenesis 33:1863–1870
112. Yin T, Getsios S, Caldelari R, Kowalczyk AP, Müller EJ, Jones JC, Green KJ (2005) Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 102:5420–5425