PKP2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPKP2, ARVD9, plakophilin 2
External IDsOMIM: 602861 MGI: 1914701 HomoloGene: 3364 GeneCards: PKP2
Orthologs
SpeciesHumanMouse
Entrez

5318

67451

Ensembl

ENSG00000057294

ENSMUSG00000041957

UniProt

Q99959

Q9CQ73

RefSeq (mRNA)

NM_004572
NM_001005242

NM_026163

RefSeq (protein)

NP_001005242
NP_004563

NP_080439

Location (UCSC)Chr 12: 32.79 – 32.9 MbChr 16: 16.03 – 16.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Plakophilin-2 is a protein that in humans is encoded by the PKP2 gene.[5][6] Plakophilin 2 is expressed in skin and cardiac muscle, where it functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiac muscle, plakophilin-2 is found in desmosome structures located within intercalated discs. Mutations in PKP2 have been shown to be causal in arrhythmogenic right ventricular cardiomyopathy.

Structure

Two splice variants of the PKP2 gene have been identified. The first has a molecular weight of 97.4 kDa (881 amino acids) and the second of molecular weight of 92.7 kDa (837 amino acids).[7][8] A processed pseudogene with high similarity to this locus has been mapped to chromosome 12p13.[6]

Plakophilin-2 is a member of the armadillo repeat and plakophilin protein family. Plakophilin proteins contain nine central, conserved armadillo repeat domains flanked by N-terminal and C-terminal domains.[9] Alternately spliced transcripts encoding protein isoforms have been identified.[10]

Plakophilin 2 localizes to cell desmosomes and nuclei and binds plakoglobin, desmoplakin, and the desmosomal cadherins via N-terminal head domain.[11][12]

Function

Plakophilin 2 functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiomyocytes, plakophilin-2 is found at desmosome structures within intercalated discs, which link adjacent sarcolemmal membranes together.[13] The desmosomal protein, desmoplakin, is the core constituent of the plaque which anchors intermediate filaments to the sarcolemma by its C-terminus and indirectly to sarcolemmal cadherins by its N-terminus, facilitated by plakoglobin and plakophilin-2.[14] Plakophilin is necessary for normal localization and content of desmoplakin to desmosomes, which may in part be due to the recruitment of protein kinase C alpha to desmoplakin.[15]

Ablation of PKP2 in mice severely disrupts normal heart morphogenesis. Mutant mice are embryonic lethal and exhibit deficits in the formation of adhering junctions in cardiomyocytes, including the dissociation of desmoplakin and formation of cytoplasmic granular aggregates around embryonic day 10.5-11. Additional malformation included reduced trabeculation, cytoskeletal disarray and cardiac wall rupture.[16] Further studies demonstrated that plakophilin-2 coordinate with E-cadherin is required to properly localize RhoA early in actin cytoskeletal rearrangement in order to properly couple the assembly of adherens junctions to the translocation of desmosome precursors in newly formed cell-cell junctions.[17]

Plakophilin-2 over time has shown to be more than components of cell-cell junctions; rather the plakophilins are emerging as versatile scaffolds for various signaling pathways that more globally modulate diverse cellular activities.[9] Plakophilin-2 has shown to localize to nuclei, in addition to desmosomal plaques in the cytoplasm. Studies have shown that plakkophillin-2 is found in the nucleoplasm, complexed in the RNA polymerase III holoenzyme with the largest subunit of RNA polymerase III, termed RPC155.[11]

There are data to support molecular crosstalk between plakophilin-2 and proteins involved in mechanical junctions in cardiomyocytes, including connexin 43, the major component of cardiac gap junctions; the voltage-gated sodium channel Na(V)1.5 and its interacting subunit, ankyrin G; and the K(ATP). Decreased expression of plakophilin-2 via siRNA leads to a decrease in and redistribution of connexin 43 protein, as well as a decrease in coupling of adjacent cardiomyocytes. Studies also showed that GJA1 and plakophilin-2 are components in the same biomolecular complex.[18] Plakophilin-2 also associates with Na(V)1.5, and knockdown of plakophilin-2 in cardiomyocytes alters sodium current properties as well as velocity of action potential propagation.[19] It has also been demonstrated that plakophilin-2 associates with an important component of the Na(V)1.5 complex, ankyrin G, and loss of ankyrin G via siRNA downregulation mislocalized plakophilin-2 and connexin 43 in cardiac cells, which was coordinate with decreased electrical coupling of cells and decreased adhesion strength.[20] These studies were further supported by an investigation in a mouse model harboring a PKP2-heterozygous null mutation, which showed decreased Na(V)1.5 amplitude, as well as a shift in gating and kinetics; pharmacological challenge also induced ventricular arrhythmias. These findings further support the notion that desmosomes crosstalk with sodium channels in the heart, and suggest that the risk of arrhythmias in patients with PKP2 mutations may be unveiled with pharmacological challenge.[21] Evidence has also shown that plakophilin-2 binds to the K(ATP) channel subunit, Kir6.2, and that in cardiomyocytes from haploinsufficient PKP2 mice, K(ATP) channel current density was ~40% smaller and regional heterogeneity of K(ATP) channels was altered, suggesting that plakophilin-2 interacts with K(ATP) and mediates crosstalk between intercellular junctions and membrane excitability.[22]

Clinical significance

Mutations in PKP2 have been associated with, have been shown to cause, and are considered common in arrhythmogenic right ventricular cardiomyopathy, which is characterized by fibrofatty replacement of cardiomyocytes, ventricular tachycardia and sudden cardiac death.[23][24][25][26][27][28][29][30] It is estimated that 70% of all mutations associated with arrhythmogenic right ventricular cardiomyopathy are within the PKP2 gene.[31] These mutations in general appear to disrupt the assembly and stability of desmosomes.[32] Mechanistic studies have shown that certain PKP2 mutations result in instability of the plakophilin-2 protein due to enhanced calpain-mediated degradation.[33]

Specific and sensitive markers of PKP2 and plakoglobin mutation carriers in arrhythmogenic right ventricular cardiomyopathy have been identified to include T-wave inversions, right ventricular wall motion abnormalities, and ventricular extrasystoles.[34] Additionally, immunohistochemical analysis of proteins comprising cardiomyocyte desmosomes has shown to be a highly sensitive and specific diagnostic indicator.[35]

Clinical and genetic characterization of arrhythmogenic right ventricular cardiomyopathy is currently under intense investigation to understand the penetrance associated with PKP2 mutations, as well as other genes encoding desmosomal proteins, in disease progression and outcome.[10][36][37][38][39][40][41][42][43][44][45]

PKP2 mutations were also found to coexist with sodium channelopathies in patients with Brugada syndrome.[46][47]

Additionally, plakophilin-2 was found in adherens junctions of cardiac myxomata tumors analyzed, and absent in patients with noncardiac myxomata, suggesting that plakophilin-2 may serve as a valuable marker in the clinical diagnosis of cardiac myxomata.[48]

Interactions

PKP2 has been shown to interact with:

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000057294 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041957 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Mertens C, Kuhn C, Franke WW (January 1997). "Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque". J Cell Biol. 135 (4): 1009–25. doi:10.1083/jcb.135.4.1009. PMC 2133394. PMID 8922383.
  6. 1 2 "Entrez Gene: PKP2 plakophilin 2".
  7. ↑ "Protein sequence of human PKP2 (Uniprot ID: Q99959)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 11 July 2015.
  8. ↑ "Protein sequence of human PKP2 (Uniprot ID: Q99959-2)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 11 July 2015.
  9. 1 2 Bass-Zubek AE, Godsel LM, Delmar M, Green KJ (October 2009). "Plakophilins: multifunctional scaffolds for adhesion and signaling". Current Opinion in Cell Biology. 21 (5): 708–16. doi:10.1016/j.ceb.2009.07.002. PMC 3091506. PMID 19674883.
  10. 1 2 Groeneweg JA, Ummels A, Mulder M, Bikker H, van der Smagt JJ, van Mil AM, Homfray T, Post JG, Elvan A, van der Heijden JF, Houweling AC, Jongbloed JD, Wilde AA, van Tintelen JP, Hauer RN, Dooijes D (November 2014). "Functional assessment of potential splice site variants in arrhythmogenic right ventricular dysplasia/cardiomyopathy". Heart Rhythm. 11 (11): 2010–7. doi:10.1016/j.hrthm.2014.07.041. PMID 25087486.
  11. 1 2 3 4 5 6 7 8 9 Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ (March 2002). "Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling". The Journal of Biological Chemistry. 277 (12): 10512–22. doi:10.1074/jbc.M108765200. PMID 11790773.
  12. ↑ Mertens C, Hofmann I, Wang Z, Teichmann M, Sepehri Chong S, Schnölzer M, Franke WW (July 2001). "Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2". Proceedings of the National Academy of Sciences of the United States of America. 98 (14): 7795–800. Bibcode:2001PNAS...98.7795M. doi:10.1073/pnas.141219498. PMC 35421. PMID 11416169.
  13. ↑ Garrod D, Chidgey M (March 2008). "Desmosome structure, composition and function". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1778 (3): 572–87. doi:10.1016/j.bbamem.2007.07.014. PMID 17854763.
  14. ↑ Jefferson JJ, Leung CL, Liem RK (July 2004). "Plakins: goliaths that link cell junctions and the cytoskeleton". Nature Reviews Molecular Cell Biology. 5 (7): 542–53. doi:10.1038/nrm1425. PMID 15232572. S2CID 32003509.
  15. ↑ Bass-Zubek AE, Hobbs RP, Amargo EV, Garcia NJ, Hsieh SN, Chen X, Wahl JK, Denning MF, Green KJ (May 2008). "Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly". The Journal of Cell Biology. 181 (4): 605–13. doi:10.1083/jcb.200712133. PMC 2386101. PMID 18474624.
  16. ↑ Grossmann KS, Grund C, Huelsken J, Behrend M, Erdmann B, Franke WW, Birchmeier W (October 2004). "Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation". The Journal of Cell Biology. 167 (1): 149–60. doi:10.1083/jcb.200402096. PMC 2172504. PMID 15479741.
  17. ↑ Godsel LM, Dubash AD, Bass-Zubek AE, Amargo EV, Klessner JL, Hobbs RP, Chen X, Green KJ (August 2010). "Plakophilin 2 couples actomyosin remodeling to desmosomal plaque assembly via RhoA". Molecular Biology of the Cell. 21 (16): 2844–59. doi:10.1091/mbc.E10-02-0131. PMC 2921118. PMID 20554761.
  18. ↑ Oxford EM, Musa H, Maass K, Coombs W, Taffet SM, Delmar M (September 2007). "Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells". Circulation Research. 101 (7): 703–11. doi:10.1161/CIRCRESAHA.107.154252. PMID 17673670.
  19. 1 2 Sato PY, Musa H, Coombs W, Guerrero-Serna G, Patiño GA, Taffet SM, Isom LL, Delmar M (September 2009). "Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes". Circulation Research. 105 (6): 523–6. doi:10.1161/CIRCRESAHA.109.201418. PMC 2742576. PMID 19661460.
  20. 1 2 Sato PY, Coombs W, Lin X, Nekrasova O, Green KJ, Isom LL, Taffet SM, Delmar M (July 2011). "Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc". Circulation Research. 109 (2): 193–201. doi:10.1161/CIRCRESAHA.111.247023. PMC 3139453. PMID 21617128.
  21. ↑ Cerrone M, Noorman M, Lin X, Chkourko H, Liang FX, van der Nagel R, Hund T, Birchmeier W, Mohler P, van Veen TA, van Rijen HV, Delmar M (September 2012). "Sodium current deficit and arrhythmogenesis in a murine model of plakophilin-2 haploinsufficiency". Cardiovascular Research. 95 (4): 460–8. doi:10.1093/cvr/cvs218. PMC 3422082. PMID 22764151.
  22. 1 2 Hong M, Bao L, Kefaloyianni E, Agullo-Pascual E, Chkourko H, Foster M, Taskin E, Zhandre M, Reid DA, Rothenberg E, Delmar M, Coetzee WA (November 2012). "Heterogeneity of ATP-sensitive K+ channels in cardiac myocytes: enrichment at the intercalated disk". The Journal of Biological Chemistry. 287 (49): 41258–67. doi:10.1074/jbc.M112.412122. PMC 3510824. PMID 23066018.
  23. ↑ Zhou X, Chen M, Song H, Wang B, Chen H, Wang J, Wang W, Feng S, Zhang F, Ju W, Li M, Gu K, Cao K, Wang DW, Yang B (April 2015). "Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with arrhythmogenic right ventricular cardiomyopathy". European Journal of Medical Genetics. 58 (4): 258–65. doi:10.1016/j.ejmg.2015.02.009. PMID 25765472.
  24. ↑ Li Mura IE, Bauce B, Nava A, Fanciulli M, Vazza G, Mazzotti E, Rigato I, De Bortoli M, Beffagna G, Lorenzon A, Calore M, Dazzo E, Nobile C, Mostacciuolo ML, Corrado D, Basso C, Daliento L, Thiene G, Rampazzo A (November 2013). "Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy". European Journal of Human Genetics. 21 (11): 1226–31. doi:10.1038/ejhg.2013.39. PMC 3798844. PMID 23486541.
  25. ↑ Zhang M, Tavora F, Oliveira JB, Li L, Franco M, Fowler D, Zhao Z, Burke A (2012). "PKP2 mutations in sudden death from arrhythmogenic right ventricular cardiomyopathy (ARVC) and sudden unexpected death with negative autopsy (SUDNA)". Circulation Journal. 76 (1): 189–94. doi:10.1253/circj.cj-11-0747. PMID 22019812.
  26. ↑ van der Zwaag PA, Cox MG, van der Werf C, Wiesfeld AC, Jongbloed JD, Dooijes D, Bikker H, Jongbloed R, Suurmeijer AJ, van den Berg MP, Hofstra RM, Hauer RN, Wilde AA, van Tintelen JP (December 2010). "Recurrent and founder mutations in the Netherlands : Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia". Netherlands Heart Journal. 18 (12): 583–91. doi:10.1007/s12471-010-0839-5. PMC 3018603. PMID 21301620.
  27. ↑ Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L (November 2004). "Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy". Nature Genetics. 36 (11): 1162–4. doi:10.1038/ng1461. PMID 15489853.
  28. ↑ Syrris P, Ward D, Asimaki A, Sen-Chowdhry S, Ebrahim HY, Evans A, Hitomi N, Norman M, Pantazis A, Shaw AL, Elliott PM, McKenna WJ (January 2006). "Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy" (PDF). Circulation. 113 (3): 356–64. doi:10.1161/CIRCULATIONAHA.105.561654. PMID 16415378. S2CID 819048.
  29. ↑ Kannankeril PJ, Bhuiyan ZA, Darbar D, Mannens MM, Wilde AA, Roden DM (August 2006). "Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a family". Heart Rhythm. 3 (8): 939–44. doi:10.1016/j.hrthm.2006.04.028. PMID 16876743.
  30. ↑ Lahtinen AM, Lehtonen A, Kaartinen M, Toivonen L, Swan H, Widén E, Lehtonen E, Lehto VP, Kontula K (May 2008). "Plakophilin-2 missense mutations in arrhythmogenic right ventricular cardiomyopathy". International Journal of Cardiology. 126 (1): 92–100. doi:10.1016/j.ijcard.2007.03.137. PMID 17521752.
  31. ↑ van Tintelen JP, Entius MM, Bhuiyan ZA, Jongbloed R, Wiesfeld AC, Wilde AA, van der Smagt J, Boven LG, Mannens MM, van Langen IM, Hofstra RM, Otterspoor LC, Doevendans PA, Rodriguez LM, van Gelder IC, Hauer RN (April 2006). "Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy". Circulation. 113 (13): 1650–8. doi:10.1161/CIRCULATIONAHA.105.609719. PMID 16567567.
  32. ↑ Hall C, Li S, Li H, Creason V, Wahl JK (2009). "Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 mutations disrupt desmosome assembly and stability". Cell Communication & Adhesion. 16 (1–3): 15–27. doi:10.1080/15419060903009329. PMID 19533476. S2CID 19077857.
  33. ↑ Kirchner F, Schuetz A, Boldt LH, Martens K, Dittmar G, Haverkamp W, Thierfelder L, Heinemann U, Gerull B (August 2012). "Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations". Circulation: Cardiovascular Genetics. 5 (4): 400–11. doi:10.1161/CIRCGENETICS.111.961854. PMID 22781308.
  34. ↑ Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, Zambartas C, Stefanadis C, McKenna WJ, Protonotarios N (September 2006). "Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis". European Heart Journal. 27 (18): 2208–16. doi:10.1093/eurheartj/ehl184. PMID 16893920.
  35. ↑ van Tintelen JP, Hauer RN (July 2009). "Cardiomyopathies: New test for arrhythmogenic right ventricular cardiomyopathy". Nature Reviews. Cardiology. 6 (7): 450–1. doi:10.1038/nrcardio.2009.97. PMID 19554004. S2CID 20454940.
  36. ↑ Cox MG, van der Zwaag PA, van der Werf C, van der Smagt JJ, Noorman M, Bhuiyan ZA, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, Dooijes D, van den Wijngaard A, Houweling AC, Jongbloed JD, Jordaens L, Cramer MJ, Doevendans PA, de Bakker JM, Wilde AA, van Tintelen JP, Hauer RN (June 2011). "Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study". Circulation. 123 (23): 2690–700. doi:10.1161/CIRCULATIONAHA.110.988287. PMID 21606396.
  37. ↑ Lahtinen AM, Lehtonen E, Marjamaa A, Kaartinen M, Heliö T, Porthan K, Oikarinen L, Toivonen L, Swan H, Jula A, Peltonen L, Palotie A, Salomaa V, Kontula K (August 2011). "Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy". Heart Rhythm. 8 (8): 1214–21. doi:10.1016/j.hrthm.2011.03.015. PMID 21397041.
  38. ↑ Sen-Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna WJ (April 2007). "Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression". Circulation. 115 (13): 1710–20. doi:10.1161/CIRCULATIONAHA.106.660241. PMID 17372169.
  39. ↑ van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD (May 2007). "Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?". Current Opinion in Cardiology. 22 (3): 185–92. doi:10.1097/HCO.0b013e3280d942c4. PMID 17413274. S2CID 24552922.
  40. ↑ Awad MM, Calkins H, Judge DP (May 2008). "Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy". Nature Clinical Practice Cardiovascular Medicine. 5 (5): 258–67. doi:10.1038/ncpcardio1182. PMC 2822988. PMID 18382419.
  41. ↑ den Haan AD, Tan BY, Zikusoka MN, Lladó LI, Jain R, Daly A, Tichnell C, James C, Amat-Alarcon N, Abraham T, Russell SD, Bluemke DA, Calkins H, Dalal D, Judge DP (October 2009). "Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy". Circulation: Cardiovascular Genetics. 2 (5): 428–35. doi:10.1161/CIRCGENETICS.109.858217. PMC 2801867. PMID 20031617.
  42. ↑ Bauce B, Nava A, Beffagna G, Basso C, Lorenzon A, Smaniotto G, De Bortoli M, Rigato I, Mazzotti E, Steriotis A, Marra MP, Towbin JA, Thiene G, Danieli GA, Rampazzo A (January 2010). "Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia". Heart Rhythm. 7 (1): 22–9. doi:10.1016/j.hrthm.2009.09.070. PMID 20129281.
  43. ↑ Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, Fontaine G, Coirault C, Frank R, Hainque B, Charron P (June 2010). "Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice". Europace. 12 (6): 861–8. doi:10.1093/europace/euq104. PMID 20400443.
  44. ↑ Gerull B (June 2014). "Skin-heart connection: what can the epidermis tell us about the myocardium in arrhythmogenic cardiomyopathy?". Circulation: Cardiovascular Genetics. 7 (3): 225–7. doi:10.1161/CIRCGENETICS.114.000647. PMID 24951656.
  45. ↑ Brun F, Barnes CV, Sinagra G, Slavov D, Barbati G, Zhu X, Graw SL, Spezzacatene A, Pinamonti B, Merlo M, Salcedo EE, Sauer WH, Taylor MR, Mestroni L (October 2014). "Titin and desmosomal genes in the natural history of arrhythmogenic right ventricular cardiomyopathy". Journal of Medical Genetics. 51 (10): 669–76. doi:10.1136/jmedgenet-2014-102591. PMC 4465780. PMID 25157032.
  46. ↑ 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 (March 2014). "Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype". Circulation. 129 (10): 1092–103. doi:10.1161/CIRCULATIONAHA.113.003077. PMC 3954430. PMID 24352520.
  47. ↑ Cerrone M, Delmar M (July 2014). "Desmosomes and the sodium channel complex: implications for arrhythmogenic cardiomyopathy and Brugada syndrome". Trends in Cardiovascular Medicine. 24 (5): 184–90. doi:10.1016/j.tcm.2014.02.001. PMC 4099253. PMID 24656989.
  48. ↑ Rickelt S, Rizzo S, Doerflinger Y, Zentgraf H, Basso C, Gerosa G, Thiene G, Moll R, Franke WW (November 2010). "A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata". Modern Pathology. 23 (11): 1429–37. doi:10.1038/modpathol.2010.138. PMID 20693980.
  49. ↑ Agullo-Pascual E, Reid DA, Keegan S, Sidhu M, Fenyö D, Rothenberg E, Delmar M (November 2013). "Super-resolution fluorescence microscopy of the cardiac connexome reveals plakophilin-2 inside the connexin43 plaque". Cardiovascular Research. 100 (2): 231–40. doi:10.1093/cvr/cvt191. PMC 3797628. PMID 23929525.

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