1,500
Views
36
CrossRef citations to date
0
Altmetric
Review Article

Desmosomal Cadherins and Signaling: Lessons from Autoimmune Disease

&
Pages 77-84 | Received 26 Nov 2013, Accepted 16 Dec 2013, Published online: 24 Jan 2014

REFERENCES

  • Amagai M, Stanley JR (2012). Desmoglein as a Target in Skin Disease and Beyond. J Invest Dermatol. 132: 776–784.
  • Aoyama Y, Kitajima Y (1999). Pemphigus vulgaris-IgG causes a rapid depletion of desmoglein 3 (Dsg3) from the Triton X-100 soluble pools, leading to the formation of Dsg3-depleted desmosomes in a human squamous carcinoma cell line, DJM-1 cells. J Invest Dermatol. 112: 67–71.
  • Bass-Zubek AE, Hobbs RP, Amargo EV, Garcia NJ, Hsieh SN, Chen X, Wahl JK III, Denning MF, Green KJ (2008). Plakophilin 2: a critical scaffold for PKCα that regulates intercellular junction assembly. J Cell Biol. 181: 605–613.
  • Bektas M, Jolly PS, Berkowitz P, Amagai M, Rubenstein DS (2013). A pathophysiologic role for epidermal growth factor receptor in pemphigus acantholysis. J Biol Chem. 288: 9447–9456.
  • Berkowitz P, Chua M, Liu Z, Diaz LA, Rubenstein DS (2008). Autoantibodies in the autoimmune disease pemphigus foliaceus induce blistering via p38 mitogen-activated protein kinase-dependent signaling in the skin. Am J Pathol. 173: 1628–1636.
  • Berkowitz P, Diaz LA, Hall RP, Rubenstein DS (2007). Induction of p38MAPK and HSP27 phosphorylation in pemphigus patient skin. J Invest Dermatol. 128: 738–740.
  • Berkowitz P, Hu P, Liu Z, Diaz LA, Enghild JJ, Chua MP, Rubenstein DS (2005). Desmosome signaling. Inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganization. J Biol Chem. 280: 23778–23784.
  • Berkowitz P, Hu P, Warren S, Liu Z, Diaz LA, Rubenstein DS (2006). p38MAPK inhibition prevents disease in pemphigus vulgaris mice. Proc Natl Acad Sci U S A. 103: 12855–12860.
  • Brennan D, Hu Y, Medhat W, Dowling A, Mahoney MG (2010). Superficial Dsg2 Expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins. Dermatol Res Pract. 2010: 410278.
  • Caldelari R, de Bruin A, Baumann D, Suter MM, Bierkamp C, Balmer V, Muller E (2001). A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris. J Cell Biol. 153: 823–834.
  • Calkins CC, Setzer SV, Jennings JM, Summers S, Tsunoda K, Amagai M, Kowalczyk AP (2006). Desmoglein endocytosis and desmosome disassembly are coordinated responses to pemphigus autoantibodies. J Biol Chem. 281: 7623–7634.
  • 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.
  • Chernyavsky AI, Arredondo J, Kitajima Y, Sato-Nagai M, Grando SA (2007). Desmoglein versus non-desmoglein signaling in pemphigus acantholysis: characterization of novel signaling pathways downstream of pemphigus vulgaris antigens. J Biol Chem. 282: 13804–13812.
  • Cirillo N, Lanza A, Prime SS (2010). Induction of hyper-adhesion attenuates autoimmune-induced keratinocyte cell-cell detachment and processing of adhesion molecules via mechanisms that involve PKC. Exp Cell Res. 316: 580–592.
  • Delva E, Jennings JM, Calkins CC, Kottke MD, Faundez V, Kowalczyk AP (2008). Pemphigus Vulgaris IgG-induced desmoglein-3 endocytosis and desmosomal disassembly are mediated by a clathrin- and dynamin-independent mechanism. J Biol Chem. 283: 18303–18313.
  • Di Zenzo G, Di Lullo G, Corti D, Calabresi V, Sinistro A, Vanzetta F, Didona B, Cianchini G, Hertl M, Eming R Amagai M, Ohyama B, Hashimoto T, Sloostra J, Sallusto F, Zambruno G, Lanzavecchia A (2012). Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface. J Clin Invest. 122: 3781–3790.
  • Esaki C, Seishima M, Yamada T, Osada K, Kitajima Y (1995). Pharmacologic evidence for involvement of phospholipase C in pemphigus IgG-induced inositol 1,4,5-trisphosphate generation, intracellular calcium increase, and plasminogen activator secretion in DJM-1 cells, a squamous cell carcinoma line. J Invest Dermatol. 105: 329–333.
  • Frusic-Zlotkin M, Raichenberg D, Wang X, David M, Michel B, Milner Y (2006). Apoptotic mechanism in pemphigus autoimmunoglobulins-induced acantholysis–possible involvement of the EGF receptor. Autoimmunity. 39: 563–575.
  • Garrod D (2010). Desmosomes In Vivo. Dermatol Res Pract. 2010: 212439.
  • Garrod DR, Berika MY, Bardsley WF, Holmes D, Tabernero L (2005). Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure. J Cell Sci. 118: 5743–5754.
  • Getsios S, Waschke J, Borradori L, Hertl M, Muller EJ (2010). From cell signaling to novel therapeutic concepts: international pemphigus meeting on advances in pemphigus research and therapy. J Invest Dermatol. 130: 1764–1768.
  • Gil MP, Modol T, España A, López-Zabalza MJ (2012). Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris. Exp Dermatol. 21: 254–259.
  • Gliem M, Heupel W-M, Spindler V, Harms GS, Waschke J (2010). Actin reorganization contributes to loss of cell adhesion in pemphigus vulgaris. Am J Physiol Cell Physiol. 299: C606–C613.
  • 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.
  • Grando S (2012). Pemphigus autoimmunity: hypotheses and realities. Autoimmunity. 45: 7–35.
  • Heupel W-M, Engerer P, Schmidt E, Waschke J (2009a). Pemphigus vulgaris IgG cause loss of desmoglein-mediated adhesion and keratinocyte dissociation independent of epidermal growth factor receptor. Am J Pathol. 174: 475–485.
  • Heupel W-M, Müller T, Efthymiadis A, Schmidt E, Drenckhahn D, Waschke J (2009b). Peptides targeting the desmoglein 3 adhesive interface prevent autoantibody-induced acantholysis in pemphigus. J Biol Chem. 284: 8589–8595.
  • Heupel WM, Zillikens D, Drenckhahn D, Waschke J (2008). Pemphigus vulgaris IgG directly inhibit desmoglein 3-mediated transinteraction. J Immunol. 181: 1825–1834.
  • Hobbs RP, Green KJ (2012). Desmoplakin regulates desmosome hyperadhesion. J Invest Dermatol. 132: 482–485.
  • Iwatsuki K, Takigawa M, Imaizumi S, Yamada M (1989). In vivo binding site of pemphigus vulgaris antibodies and their fate during acantholysis. J Am Acad Dermatol. 20: 578–582.
  • Jolly PS, Berkowitz P, Bektas M, Lee H-E, 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.
  • Kimura TE, Merritt AJ, Garrod DR (2007). Calcium-independent desmosomes of keratinocytes are hyper-adhesive. J Invest Dermatol. 127: 775–781.
  • Kitajima Y (2013). New insights into desmosome regulation and pemphigus blistering as a desmosome-remodeling disease. Kaohsiung J Med Sci. 29: 1–13.
  • Kneisel A, Hertl M (2011). Autoimmune bullous skin diseases. Part 1: Clinical manifestations.J Dtsch Dermatol Ges. 9: 844–857.
  • Kröger C, Loschke F, Schwarz N, Windoffer R, Leube RE, Magin TM (2013). Keratins control intercellular adhesion involving PKC-α–mediated desmoplakin phosphorylation. J Cell Biol. 201: 681–692.
  • Lanza A, Cirillo N, Rossiello R, Rienzo M, Cutillo L, Casamassimi A, de Nigris F, Schiano C, Rossiello L, Femiano F Gombos F, Napoli C (2008). Evidence of key role of Cdk2 overexpression in pemphigus vulgaris. J Biol Chem. 283: 8736–8745.
  • Li N, Zhao M, Wang J, Liu Z, Diaz LA (2009). Involvement of the apoptotic mechanism in pemphigus foliaceus autoimmune injury of the skin. J Immunol. 182: 711–717.
  • Mao X, Choi EJ, Payne AS (2009). Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies. J Invest Dermatol. 129: 908–18.
  • Mao X, Li H, Sano Y, Gaestel M, Mo Park J, Payne AS (2013). MAPKAP Kinase 2 (MK2)-dependent and -independent models of blister formation in pemphigus vulgaris. J Invest Dermatol.
  • Mao X, Nagler AR, Farber SA, Choi EJ, Jackson LH, Leiferman KM, Ishii N, Hashimoto T, Amagai M, Zone JJ, Payne AS (2010). Autoimmunity to desmocollin 3 in pemphigus vulgaris. Am J Pathol. 177: 2724–2730.
  • Marchenko S, Chernyavsky AI, Arredondo J, Gindi V, Grando SA (2010). Antimitochondrial autoantibodies in pemphigus vulgaris. J Biol Chem. 285: 3695–3704.
  • Meng J-J, Bornslaeger EA, Green KJ, Steinert PM, Ip W (1997). Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments. J Biol Chem. 272: 21495–21503.
  • Müller EJ, Williamson L, Kolly C, Suter MM (2008). Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation?J Invest Dermatol. 128: 501–516.
  • Nekrasova O, Green KJ (2013). Desmosome assembly and dynamics. Trends Cell Biol. 23: 537–546.
  • Nekrasova OE, Amargo EV, Smith WO, Chen J, Kreitzer GE, Green KJ (2011). Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes. J Cell Biol. 195: 1185–1203.
  • Nguyen B, Dusek RL, Beaudry VG, Marinkovich MP, Attardi LD (2009). Loss of the desmosomal protein perp enhances the phenotypic effects of pemphigus vulgaris autoantibodies. J Invest Dermatol. 129: 1710–1718.
  • Oktarina DAM, van der Wier G, Diercks GFH, Jonkman MF, Pas HH (2011). IgG-induced clustering of desmogleins 1 and 3 in skin of patients with pemphigus fits with the desmoglein nonassembly depletion hypothesis. Br J Dermatol. 165: 552–562.
  • Osada K, Seishima M, Kitajima Y (1997). Pemphigus IgG activates and translocates protein kinase C from the cytosol to the particulate/cytoskeleton fractions in human keratinocytes. J Invest Dermatol. 108: 482–487.
  • Patel HP, Diaz LA, Anhalt GJ, Labib RS, Takahashi Y (1984). Demonstration of pemphigus antibodies on the cell surface of murine epidermal cell monolayers and their internalization. J Invest Dermatol. 83: 409–415.
  • Pretel M, España A, Marquina M, Beatriz Pelacho López-Picazo J, López-Zabalza J (2009). An imbalance in Akt/mTOR is involved in the apoptotic and acantholytic processes in a mouse model of pemphigus vulgaris. Exp Dermatol. 18: 771–780.
  • Rafei D, Müller R, Ishii N, Llamazares M, Hashimoto T, Hertl M, Eming R (2011). IgG autoantibodies against desmocollin 3 in pemphigus sera induce loss of keratinocyte adhesion. Am J Pathol. 178: 718–723.
  • Roetzer V, Waschke J, Spindler V (2013). Adducin modulates intercellular keratinocyte adhesion. FASEB J. 27: 650.15.
  • 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.
  • Sato M, Aoyama Y, Kitajima Y (2000). Assembly pathway of desmoglein 3 to desmosomes and its perturbation by pemphigus vulgaris-IgG in cultured keratinocytes, as revealed by time-lapsed labeling immunoelectron microscopy. Lab Invest. 80: 1583–1592.
  • Schmidt E, Waschke J (2009). Apoptosis in pemphigus. Autoimmun Rev. 8: 533–537.
  • Schulze K, Galichet A, Sayar BS, Scothern A, Howald D, Zymann H, Siffert M, Zenhausern D, Bolli R, Koch PJ Garrod D, Suter MM, Müller EJ (2012). An adult passive transfer mouse model to study desmoglein 3 signaling in pemphigus vulgaris. J Invest Dermatol. 132: 346–355.
  • Seishima M, Esaki C, Osada K, Mori S, Hashimoto T, Kitajima Y (1995). Pemphigus IgG, but not bullous pemphigoid IgG, causes a transient increase in intracellular calcium and inositol 1,4,5-triphosphate in DJM-1 cells, a squamous cell carcinoma line. J Invest Dermatol. 104: 33–37.
  • Shu E, Yamamoto Y, Aoyama Y, Kitajima Y (2007). Intraperitoneal injection of pemphigus vulgaris-IgG into mouse depletes epidermal keratinocytes of desmoglein 3 associated with generation of acantholysis. Arch Derm Res. 299: 165–167.
  • Spindler V, Drenckhahn D, Zillikens D, Waschke J (2007). Pemphigus IgG causes skin splitting in the presence of both desmoglein 1 and desmoglein 3. Am J Pathol. 171: 906–16.
  • Spindler V, Endlich A, Hartlieb E, Vielmuth F, Schmidt E, Waschke J (2011). The extent of desmoglein 3 depletion in pemphigus vulgaris is dependent on Ca(2+)-induced differentiation: a role in suprabasal epidermal skin splitting?Am J Pathol. 179: 1905–16.
  • Spindler V, Rotzer V, Dehner C, Kempf B, Gliem M, Radeva M, Hartlieb E, Harms GS, Schmidt E, Waschke J (2013). Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering. J Clin Invest. 123: 800–811.
  • Takahashi Y, Patel HP, Labib RS, Diaz LA, Anhalt GJ (1985). Experimentally induced pemphigus vulgaris in neonatal BALB/c mice: a time-course study of clinical, immunologic, ultrastructural, and cytochemical changes. J Invest Dermatol. 84: 41–6.
  • Thomason HA, Cooper NH, Ansell DM, Chiu M, Merrit AJ, Hardman MJ, Garrod DR (2012). Direct evidence that PKCα positively regulates wound re-epithelialization: correlation with changes in desmosomal adhesiveness. J Pathol. 227: 346–356.
  • Thomason HA, Scothern A, McHarg S, Garrod DR (2010). Desmosomes: adhesive strength and signalling in health and disease. Biochem J. 429: 419–433.
  • Tsang SM, Brown L, Gadmor H, Gammon L, Fortune F, Wheeler A, Wan H (2012a). Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics. Exp Cell Res. 318: 2269–2283.
  • Tsang SM, Brown L, Lin K, Liu L, Piper K, O’Toole EA, Grose R, Hart IR, Garrod DR, Fortune F, Wan H (2012b). 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.
  • Wallis S, Lloyd S, Wise I, Ireland G, Fleming TP, Garrod D (2000). The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells. Mol Biol Cell. 11: 1077–1092.
  • Waschke J (2008). The desmosome and pemphigus. Histochem Cell Biol. 130: 21–54.
  • Waschke J, Bruggeman P, Baumgartner W, Zillikens D, Drenckhahn D (2005). Pemphigus foliaceus IgG causes dissociation of desmoglein 1-containing junctions without blocking desmoglein 1 transinteraction. J Clin Invest. 115: 3157–3165.
  • Waschke J, Spindler V, Bruggeman P, Zillikens D, Schmidt G, Drenckhahn D (2006). Inhibition of Rho A activity causes pemphigus skin blistering. J Cell Biol. 175: 721–727.
  • Williamson L, Raess NA, Caldelari R, Zakher A, de Bruin A, Posthaus H, Bolli R, Hunziker T, Suter MM, Muller EJ (2006). Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin. EMBO J. 25: 3298–309.
  • Windoffer R, Borchert-Stuhltrager M, Leube RE (2002). Desmosomes: interconnected calcium-dependent structures of remarkable stability with significant integral membrane protein turnover. J Cell Sci. 115: 1717–1732.
  • Yamagami J, Payne AS, Kacir S, Ishii K, Siegel DL, Stanley JR (2010). Homologous regions of autoantibody heavy chain complementarity-determining region 3 (H-CDR3) in patients with pemphigus cause pathogenicity. J Clin Invest. 120: 4111–4117.
  • Yamamoto Y, Aoyama Y, Shu E, Tsunoda K, Amagai M, Kitajima Y (2007). Anti-desmoglein 3 (Dsg3) Monoclonal antibodies deplete desmosomes of Dsg3 and differ in their Dsg3-depleting activities related to pathogenicity. J Biol Chem. 282: 17866–17876.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.