Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro

References

• Schlegel N, Boerner K, Waschke J. Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases-Lessons from experimental models and patients. Acta Physiol. 2021;231(1):361. doi:10.1111/apha.13492.
   Web of Science ®Google Scholar
• Luissint AC, Parkos CA, Nusrat A. Inflammation and the intestinal barrier: leukocyte-epithelial cell interactions, cell junction remodeling, and mucosal repair. Gastroenterology. 2016;151(4):616–379. doi:10.1053/j.gastro.2016.07.008.
   PubMed Web of Science ®Google Scholar
• Fortea M, Albert-Bayo M, Abril-Gil M, Ganda Mall J-P, Serra-Ruiz X, Henao-Paez A, Expósito E, González-Castro AM, Guagnozzi D, Lobo B, et al. Present and Future Therapeutic Approaches to Barrier Dysfunction. Front Nutr. 2021;8:718093. doi:10.3389/fnut.2021.718093.
   PubMed Web of Science ®Google Scholar
• Zuo L, Kuo WT, Turner JR. Tight junctions as targets and effectors of mucosal immune homeostasis. Cell Mol Gastroenterol Hepatol. 2020;10(2):327–340. doi:10.1016/j.jcmgh.2020.04.001.
   PubMed Web of Science ®Google Scholar
• Gross A, Pack LAP, Schacht GM, Kant S, Ungewiss H, Meir M, Schlegel N, Preisinger C, Boor P, Guldiken N, et al. Desmoglein 2, but not desmocollin 2, protects intestinal epithelia from injury. Mucosal Immunol. 2018;11(6):1630–1639. doi:10.1038/s41385-018-0062-z. Epub 2018 Aug 16; PMID 30115995.
   PubMed Web of Science ®Google Scholar
• Spindler V, Meir M, Vigh B, Flemming S, Hütz K, Germer C-T, Waschke J, Schlegel N. Loss of Desmoglein 2 Contributes to the Pathogenesis of Crohn’s Disease. Inflamm Bowel Dis. 2015;21(10):2349–2359. doi:10.1097/MIB.0000000000000486.
   PubMed Web of Science ®Google Scholar
• Meir M, Burkard N, Ungewiß H, Diefenbacher M, Flemming S, Kannapin F, Germer C-T, Schweinlin M, Metzger M, Waschke J, et al. Neurotrophic factor GDNF regulates intestinal barrier function in inflammatory bowel disease. J Clin Invest. 2019;129(7):2824–2840. doi:10.1172/JCI120261.
   PubMed Web of Science ®Google Scholar
• Nava P, Laukoetter MG, Hopkins AM, Laur O, Gerner-Smidt K, Green KJ, Parkos CA, Nusrat A. Desmoglein-2: a novel regulator of apoptosis in the intestinal epithelium. Mol Biol Cell. 2007;18(11):4565–4578. doi:10.1091/mbc.e07-05-0426.
   PubMed Web of Science ®Google Scholar
• Burkard N, Meir M, Kannapin F, Otto C, Petzke M, Germer C-T, Waschke J, Schlegel N. Desmoglein2 regulates claudin2 expression by sequestering PI-3-kinase in intestinal epithelial cells. Front Immunol. 2021;12:756321. doi:10.3389/fimmu.2021.756321.
   PubMed Web of Science ®Google Scholar
• Green KJ, Roth-Carter Q, Niessen CM, Nichols SA. Tracing the evolutionary origin of desmosomes. Curr Biol. 2020;30(10):R535–R543. doi:10.1016/j.cub.2020.03.047.
   PubMed Web of Science ®Google Scholar
• Hofmann I. Plakophilins and their roles in diseased states. Cell Tissue Res. 2020;379(1):5–12. doi:10.1007/s00441-019-03153-0.
   PubMed Web of Science ®Google Scholar
• Fuchs M, Foresti M, Radeva MY, Kugelmann D, Keil R, Hatzfeld M, Spindler V, Waschke J, Vielmuth F. Plakophilin 1 but not plakophilin 3 regulates desmoglein clustering. Cell Mol Life Sci. 2019;76(17):3465–3476. doi:10.1007/s00018-019-03083-8.
   PubMed Web of Science ®Google Scholar
• Bonne S, Gilbert B, Hatzfeld M, Chen X, Green KJ, van Roy F. Defining desmosomal plakophilin-3 interactions. J Cell Biol. 2003;161(2):403–416. doi:10.1083/jcb.200303036.
   PubMed Web of Science ®Google Scholar
• Tsatsopoulou AA, Protonotarios NI, McKenna WJ. Arrhythmogenic right ventricular dysplasia, a cell adhesion cardiomyopathy: insights into disease pathogenesis from preliminary genotype–phenotype assessment. Heart. 2006;92(12):1720–1723. doi:10.1136/hrt.2005.081679.
   PubMed Web of Science ®Google Scholar
• Furukawa C, Daigo Y, Ishikawa N, Kato T, Ito T, Tsuchiya E, Sone S, Nakamura Y. Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Cancer Res. 2005;65(16):7102–7110. doi:10.1158/0008-5472.CAN-04-1877.
   PubMed Web of Science ®Google Scholar
• Kundu ST, Gosavi P, Khapare N, Patel R, Hosing AS, Maru GB, Ingle A, DeCaprio JA, Dalal SN. Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis. Int J Cancer. 2008;123(10):2303–2314. doi:10.1002/ijc.23797.
   PubMed Web of Science ®Google Scholar
• Egu DT, Kugelmann D, Waschke J. Role of PKC and ERK signaling in epidermal blistering and desmosome regulation in pemphigus. Front Immunol. 2019;10:2883. doi:10.3389/fimmu.2019.02883.
   PubMed Web of Science ®Google Scholar
• Meir M, Salm J, Fey C, Schweinlin M, Kollmann C, Kannapin F, Germer C-T, Waschke J, Beck C, Burkard N, et al. Enteroids generated from patients with severe inflammation in crohn’s disease maintain alterations of junctional proteins. J Crohn's Colitis. 2020;14(10):1473–1487. doi:10.1093/ecco-jcc/jjaa085.
   Google Scholar
• Schlegel N, Meir M, Heupel W-M, Holthöfer B, Leube RE, Waschke J. Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity. Am J Physiol Gastrointest Liver Physiol. 2010;298(5):G774–83. doi:10.1152/ajpgi.00239.2009.
   PubMed Web of Science ®Google Scholar
• Bass-Zubek AE, Hobbs RP, Amargo EV, Garcia NJ, Hsieh SN, Chen X, Wahl JK, Denning MF, Green KJ. Plakophilin 2: a critical scaffold for PKCα that regulates intercellular junction assembly. J Cell Biol. 2008;181(4):605–613. doi:10.1083/jcb.200712133.
   PubMed Web of Science ®Google Scholar
• Keil R, Rietscher K, Hatzfeld M. Antagonistic regulation of intercellular cohesion by plakophilins 1 and 3. J Invest Dermatol. 2016;136(10):2022–2029. doi:10.1016/j.jid.2016.05.124.
   PubMed Web of Science ®Google Scholar
• Rietscher K, Wolf A, Hause G, Rother A, Keil R, Magin TM, Glass M, Niessen CM, Hatzfeld M. Growth retardation, loss of desmosomal adhesion, and impaired tight junction function identify a unique role of plakophilin 1 in vivo. J Invest Dermatol. 2016;136(7):1471–1478. doi:10.1016/j.jid.2016.03.021.
   PubMed Web of Science ®Google Scholar
• Meir M, Kannapin F, Diefenbacher M, Ghoreishi Y, Kollmann C, Flemming S, Germer C-T, Waschke J, Leven P, Schneider R, et al. Intestinal epithelial barrier maturation by enteric glial cells is GDNF-dependent. Int J Mol Sci. 2021;22(4):1887. doi:10.3390/ijms22041887.
   PubMed Web of Science ®Google Scholar
• Jiang K, Rankin CR, Nava P, Sumagin R, Kamekura R, Stowell SR, Feng M, Parkos CA, Nusrat A. Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion. J Biol Chem. 2014;289(15):10510–10517. doi:10.1074/jbc.M113.538538.
   PubMed Web of Science ®Google Scholar
• Kamekura R, Kolegraff KN, Nava P, Hilgarth RS, Feng M, Parkos CA, Nusrat A. Loss of the desmosomal cadherin desmoglein-2 suppresses colon cancer cell proliferation through EGFR signaling. Oncogene. 2014;33(36):4531–4536. doi:10.1038/onc.2013.442.
   PubMed Web of Science ®Google Scholar
• Kamekura R, Nava P, Feng M, Quiros M, Nishio H, Weber DA, Parkos CA, Nusrat A. Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier. Mol Biol Cell. 2015;26(18):3165–3177. doi:10.1091/mbc.e15-03-0147.
   PubMed Web of Science ®Google Scholar
• Borrmann CM, Mertens C, SCHMIDT A, LANGBEIN L, Kuhn C, FRANKE WW. Molecular diversity of plaques of epithelial-adhering junctions. Ann N Y Acad Sci. 2006;915(1):144–150. doi:10.1111/j.1749-6632.2000.tb05237.x.
   Google Scholar
• Gassler N, Rohr C, Schneider A, Kartenbeck J, Bach A, Obermüller N, Otto HF, Autschbach F. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am J Physiol Gastrointest Liver Physiol. 2001;281(1):G216–28. doi:10.1152/ajpgi.2001.281.1.G216.
   PubMed Web of Science ®Google Scholar
• Schmidt A, Langbein L, Prätzel S, Rode M, Rackwitz HR, Franke WW. Plakophilin 3--a novel cell-type-specific desmosomal plaque protein. Differentiation; Research in Biological Diversity. 1999;64(5):291–306. doi:10.1046/j.1432-0436.1999.6450291.x.
   PubMed Web of Science ®Google Scholar
• Gomez-Morales M, Cámara-Pulido M, Miranda-León MT, Sánchez-Palencia A, Boyero L, Gómez-Capilla JA, Fárez-Vidal ME. Differential immunohistochemical localization of desmosomal plaque-related proteins in non-small-cell lung cancer. Histopathology. 2013;63(1):103–113. doi:10.1111/his.12126.
   PubMed Web of Science ®Google Scholar
• Wilson SS, Mayo M, Melim T, Knight H, Patnaude L, Wu X, Phillips L, Westmoreland S, Dunstan R, Fiebiger E, et al. Optimized culture conditions for improved growth and functional differentiation of mouse and human colon organoids. Front Immunol. 2021;11:547102. doi:10.3389/fimmu.2020.547102.
   PubMed Web of Science ®Google Scholar
• Fulle JB, Huppert H, Liebl D, Liu J, Alves de Almeida R, Yanes B, Wright GD, Lane EB, Garrod DR, Ballestrem C, et al. Desmosome dualism – most of the junction is stable, but a plakophilin moiety is persistently dynamic. J Cell Sci. 2021;134(21). doi:10.1242/jcs.258906.
   PubMed Web of Science ®Google Scholar
• Indra I, Troyanovsky RB, Green KJ, Troyanovsky SM. Plakophilin 3 and Par3 facilitate desmosomes’ association with the apical junctional complex. Mol Biol Cell. 2021;32(19):1824–1837. doi:10.1091/mbc.E21-01-0001.
   PubMed Web of Science ®Google Scholar
• Sklyarova T, van Hengel J, Van Wonterghem E, Libert C, van Roy F, Vandenbroucke RE. Hematopoietic plakophilin-3 regulates acute tissue-specific and systemic inflammation in mice. Eur J Immunol. 2015;45(10):2898–2910. doi:10.1002/eji.201445440.
   PubMed Web of Science ®Google Scholar
• Fisher-Keso R, Breuninger S, Hofmann S, Henn M, Röhrig T, Ströbel P, Stoecklin G, Hofmann I. Plakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal proteins. Mol Cell Biol. 2014;34(23):4244–4256. doi:10.1128/MCB.00766-14.
   PubMed Web of Science ®Google Scholar
• Flemming S, Luissint A-C, Kusters DHM, Raya-Sandino A, Fan S, Zhou DW, Hasegawa M, Garcia-Hernandez V, García AJ, Parkos CA, et al. Desmocollin-2 promotes intestinal mucosal repair by controlling integrin-dependent cell adhesion and migration. Mol Biol Cell. 2020;31(6):407–418. doi:10.1091/mbc.E19-12-0692.
   PubMed Web of Science ®Google Scholar
• Broussard JA, Jaiganesh A, Zarkoob H, Conway DE, Dunn AR, Espinosa HD, Janmey PA, Green KJ. Scaling up single-cell mechanics to multicellular tissues – the role of the intermediate filament–desmosome network. J Cell Sci. 2020;133(6). doi:10.1242/jcs.228031.
   PubMed Web of Science ®Google Scholar
• Sasaki K, Kojitani N, Hirose H, Yoshihama Y, Suzuki H, Shimada M, Takayanagi A, Yamashita A, Nakaya M-A, Hirano H, et al. Shank2 binds to aPKC and controls tight junction formation with Rap1 signaling during establishment of epithelial cell polarity. Cell Rep. 2020;31(1):107407. doi:10.1016/j.celrep.2020.02.088.
   PubMed Web of Science ®Google Scholar
• Suzuki T, Elias BC, Seth A, Shen L, Turner JR, Giorgianni F, Desiderio D, Guntaka R, Rao R. PKCη regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci U S A. 2009;106(1):61–66. doi:10.1073/pnas.0802741106.
   PubMed Web of Science ®Google Scholar