Disease mutations in desmoplakin inhibit Cx43 membrane targeting mediated by desmoplakin-EB1 interactions

Journal of Cell Biology

Volumn 206, Issue 6, 2014, Pages 779-797

  Patel, Dipal M ^a   Dubash, Adi D ^a   Kreitzer, Geri ^b   Green, Kathleen J ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING PROTEIN; CX43 PROTEIN; DESMOPLAKIN; MEMBRANE PROTEIN; MICROTUBULE BINDING PROTEIN END BINDING 1; UNCLASSIFIED DRUG; CONNEXIN 43; DEMECOLCINE; DESMOGLEIN 2; DSG2 PROTEIN, HUMAN; MAPRE1 PROTEIN, HUMAN; MICROTUBULE ASSOCIATED PROTEIN; SMALL INTERFERING RNA; TUBULIN MODULATOR;

ARRHYTHMOGENIC CARDIOMYOPATHY; ARTICLE; CARDIOMYOPATHY; CELL COMMUNICATION; CONTROLLED STUDY; EMBRYO; GAP JUNCTION; GENE MUTATION; HUMAN; HUMAN CELL; MICROTUBULE ASSEMBLY; MOLECULAR DYNAMICS; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; SKIN DISEASE; SKIN FRAGILITY; ANIMAL; CELL LINE; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; DESMOSOME; GENETICS; HEART RIGHT VENTRICLE DYSPLASIA; HEK293 CELL LINE; METABOLISM; MICROTUBULE; MORPHOGENESIS; MUTATION; PATHOLOGY; PHYSIOLOGY; RAT; RNA INTERFERENCE; SPRAGUE DAWLEY RAT;

ANIMALS; ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA; CELL COMMUNICATION; CELL LINE; CERCOPITHECUS AETHIOPS; CONNEXIN 43; COS CELLS; DEMECOLCINE; DESMOGLEIN 2; DESMOPLAKINS; DESMOSOMES; GAP JUNCTIONS; HEK293 CELLS; HUMANS; MICROTUBULE-ASSOCIATED PROTEINS; MICROTUBULES; MORPHOGENESIS; MUTATION; RATS; RATS, SPRAGUE-DAWLEY; RNA INTERFERENCE; RNA, SMALL INTERFERING; TUBULIN MODULATORS;

EID: 84907064977     PISSN: 00219525     EISSN: 15408140     Source Type: Journal    
DOI: 10.1083/jcb.201312110     Document Type: Article

References (83)

1. Al-Jassar, C., T. Knowles, M. Jeeves, K. Kami, E. Behr, H. Bikker, M. Overduin, and M. Chidgey. 2011. The nonlinear structure of the desmoplakin plakin domain and the effects of cardiomyopathy-linked mutations. J. Mol. Biol. 411:1049-1061. http://dx.doi.org/10.1016/j.jmb.2011.06.047
2. Angst, B.D., L.A. Nilles, and K.J. Green. 1990. Desmoplakin II expression is not restricted to stratified epithelia. J. Cell Sci. 97:247-257.
3. Applegate, K.T., S. Besson, A. Matov, M.H. Bagonis, K. Jaqaman, and G. Danuser. 2011. plusTipTracker: Quantitative image analysis software for the measurement of microtubule dynamics. J. Struct. Biol. 176:168-184. http://dx.doi.org/10.1016/j.jsb.2011.07.009
4. Asimaki, A., P. Syrris, D. Ward, L.G. Guereta, J.E. Saffitz, and W.J. McKenna. 2009. Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy related to novel desmoplakin mutations. J. Cutan. Pathol. 36:553-559. http://dx.doi.org/10.1111/j.1600-0560.2008.01112.x
5. Basso, C., E. Czarnowska, M. Della Barbera, B. Bauce, G. Beffagna, E.K. Wlodarska, K. Pilichou, A. Ramondo, A. Lorenzon, O. Wozniek, et al. 2006. Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. Eur. Heart J. 27:1847-1854. http://dx.doi.org/10.1093/eurheartj/ehl095
6. Basso, C., B. Bauce, D. Corrado, and G. Thiene. 2012. Pathophysiology of arrhythmogenic cardiomyopathy. Nat. Rev. Cardiol. 9:223-233. http://dx.doi.org/10.1038/nrcardio.2011.173
7. Bass-Zubek, A.E., R.P. Hobbs, E.V. Amargo, N.J. Garcia, S.N. Hsieh, X. Chen, J.K. Wahl III, M.F. Denning, and K.J. Green. 2008. Plakophilin 2: a critical scaffold for PKCα that regulates intercellular junction assembly. J. Cell Biol. 181:605-613. http://dx.doi.org/10.1083/jcb.200712133
8. Bauce, B., A. Rampazzo, C. Basso, E. Mazzotti, I. Rigato, A. Steriotis, G. Beffagna, A. Lorenzon, M. De Bortoli, K. Pilichou, et al. 2011. Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations. Heart Rhythm. 8:1686-1695. http://dx.doi.org/10.1016/j.hrthm.2011.06.026
9. Bornslaeger, E.A., C.M. Corcoran, T.S. Stappenbeck, and K.J. Green. 1996. Breaking the connection: displacement of the desmosomal plaque protein desmoplakin from cell-cell interfaces disrupts anchorage of intermediate filament bundles and alters intercellular junction assembly. J. Cell Biol. 134:985-1001. http://dx.doi.org/10.1083/jcb.134.4.985
10. Borrmann, C.M., C. Grund, C. Kuhn, I. Hofmann, S. Pieperhoff, and W.W. Franke. 2006. The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur. J. Cell Biol. 85:469-485. http://dx.doi.org/10.1016/j.ejcb.2006.02.009
11. Cabral, R.M., D. Tattersall, V. Patel, G.D. McPhail, E. Hatzimasoura, D.J. Abrams, A.P. South, and D.P. Kelsell. 2012. The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes. J. Cell Sci. 125:2853-2861. http://dx.doi.org/10.1242/jcs.084152
12. Chausovsky, A., A.D. Bershadsky, and G.G. Borisy. 2000. Cadherin-mediated regulation of microtubule dynamics. Nat. Cell Biol. 2:797-804. http://dx.doi.org/10.1038/35041037
13. Chkourko, H.S., G. Guerrero-Serna, X. Lin, N. Darwish, J.R. Pohlmann, K.E. Cook, J.R. Martens, E. Rothenberg, H. Musa, and M. Delmar. 2012. Remodeling of mechanical junctions and of microtubule-associated proteins accompany cardiac connexin43 lateralization. Heart Rhythm. 9:1133- 1140. http://dx.doi.org/10.1016/j.hrthm.2012.03.003
14. Choi, H.J., and W.I. Weis. 2011. Crystal structure of a rigid four-spectrin-repeat fragment of the human desmoplakin plakin domain. J. Mol. Biol. 409:800- 812. http://dx.doi.org/10.1016/j.jmb.2011.04.046
15. Claycomb, W.C., N.A. Lanson Jr., B.S. Stallworth, D.B. Egeland, J.B. Delcarpio, A. Bahinski, and N.J. Izzo Jr. 1998. HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc. Natl. Acad. Sci. USA. 95:2979-2984. http://dx.doi.org/10.1073/pnas.95.6.2979
16. Cowin, P., and B. Burke. 1996. Cytoskeleton-membrane interactions. Curr. Opin. Cell Biol. 8:56-65. http://dx.doi.org/10.1016/S0955-0674(96)80049-4
17. Cox, M.G., P.A. van der Zwaag, C. van der Werf, J.J. van der Smagt, M. Noorman, Z.A. Bhuiyan, A.C. Wiesfeld, P.G. Volders, I.M. van Langen, D.E. Atsma, et al. 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. 123:2690- 2700. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.988287
18. Delmar, M., and W.J. McKenna. 2010. The cardiac desmosome and arrhythmogenic cardiomyopathies: from gene to disease. Circ. Res. 107:700-714. http://dx.doi.org/10.1161/CIRCRESAHA.110.223412
19. Franke, W.W., C.M. Borrmann, C. Grund, and S. Pieperhoff. 2006. The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur. J. Cell Biol. 85:69-82. http://dx.doi.org/10.1016/j.ejcb.2005.11.003
20. Fredriksson, S., M. Gullberg, J. Jarvius, C. Olsson, K. Pietras, S.M. Gu´stafsdo´ttir, A. Ostman, and U. Landegren. 2002. Protein detection using proximitydependent DNA ligation assays. Nat. Biotechnol. 20:473-477. http://dx.doi.org/10.1038/nbt0502-473
21. Galjart, N. 2010. Plus-end-tracking proteins and their interactions at microtubule ends. Curr. Biol. 20:R528-R537. http://dx.doi.org/10.1016/j.cub.2010.05.022
22. Gallicano, G.I., P. Kouklis, C. Bauer, M. Yin, V. Vasioukhin, L. Degenstein, and E. Fuchs. 1998. Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J. Cell Biol. 143:2009-2022. http://dx.doi.org/10.1083/jcb.143.7.2009
23. Getsios, S., C.L. Simpson, S. Kojima, R. Harmon, L.J. Sheu, R.L. Dusek, M. Cornwell, and K.J. Green. 2009. Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. J. Cell Biol. 185:1243-1258. http://dx.doi.org/10.1083/jcb.200809044
24. Godsel, L.M., S.N. Hsieh, E.V. Amargo, A.E. Bass, L.T. Pascoe-McGillicuddy, A.C. Huen, M.E. Thorne, C.A. Gaudry, J.K. Park, K. Myung, et al. 2005. Desmoplakin assembly dynamics in four dimensions: multiple phases differentially regulated by intermediate filaments and actin. J. Cell Biol. 171:1045-1059. http://dx.doi.org/10.1083/jcb.200510038
25. Gomes, J., M. Finlay, A.K. Ahmed, E.J. Ciaccio, A. Asimaki, J.E. Saffitz, G. Quarta, M. Nobles, P. Syrris, S. Chaubey, et al. 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. http://dx.doi.org/ 10.1093/eurheartj/ehr472
26. Green, K.J., and C.L. Simpson. 2007. Desmosomes: new perspectives on a classic. J. Invest. Dermatol. 127:2499-2515. http://dx.doi.org/10.1038/sj.jid.5701015
27. Green, K.J., D.A. Parry, P.M. Steinert, M.L. Virata, R.M. Wagner, B.D. Angst, and L.A. Nilles. 1990. Structure of the human desmoplakins. Implications for function in the desmosomal plaque. J. Biol. Chem. 265:2603-2612.
28. Grigoriev, I., S.M. Gouveia, B. van der Vaart, J. Demmers, J.T. Smyth, S. Honnappa, D. Splinter, M.O. Steinmetz, J.W. Putney Jr., C.C. Hoogenraad, and A. Akhmanova. 2008. STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER. Curr. Biol. 18:177-182. http://dx.doi.org/10.1016/j.cub.2007.12.050
29. Gundersen, G.G., E.R. Gomes, and Y. Wen. 2004. Cortical control of microtubule stability and polarization. Curr. Opin. Cell Biol. 16:106-112. http://dx.doi.org/10.1016/j.ceb.2003.11.010
30. Harmon, R.M., C.L. Simpson, J.L. Johnson, J.L. Koetsier, A.D. Dubash, N.A. Najor, O. Sarig, E. Sprecher, and K.J. Green. 2013. Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation. J. Clin. Invest. 123:1556-1570. http://dx.doi.org/10.1172/JCI65220
31. Hayashi, I., and M. Ikura. 2003. Crystal structure of the amino-terminal microtubule-binding domain of end-binding protein 1 (EB1). J. Biol. Chem. 278:36430-36434. http://dx.doi.org/10.1074/jbc.M305773200
32. Hudson, T.Y., L. Fontao, L.M. Godsel, H.J. Choi, A.C. Huen, L. Borradori, W.I. Weis, and K.J. Green. 2004. In vitro methods for investigating desmoplakin-intermediate filament interactions and their role in adhesive strength. Methods Cell Biol. 78:757-786. http://dx.doi.org/10.1016/ S0091-679X(04)78026-7
33. Huen, A.C., J.K. Park, L.M. Godsel, X. Chen, L.J. Bannon, E.V. Amargo, T.Y. Hudson, A.K. Mongiu, I.M. Leigh, D.P. Kelsell, et al. 2002. Intermediate filament-membrane attachments function synergistically with actindependent contacts to regulate intercellular adhesive strength. J. Cell Biol. 159:1005-1017. http://dx.doi.org/10.1083/jcb.200206098
34. Jamora, C., and E. Fuchs. 2002. Intercellular adhesion, signalling and the cytoskeleton. Nat. Cell Biol. 4:E101-E108. http://dx.doi.org/10.1038/ncb0402-e101
35. Jaqaman, K., D. Loerke, M. Mettlen, H. Kuwata, S. Grinstein, S.L. Schmid, and G. Danuser. 2008. Robust single-particle tracking in live-cell timelapse sequences. Nat. Methods. 5:695-702. http://dx.doi.org/10.1038/ nmeth.1237
36. Jordan, K., J.L. Solan, M. Dominguez, M. Sia, A. Hand, P.D. Lampe, and D.W. Laird. 1999. Trafficking, assembly, and function of a connexin43-green fluorescent protein chimera in live mammalian cells. Mol. Biol. Cell. 10:2033-2050. http://dx.doi.org/10.1091/mbc.10.6.2033
37. Kaplan, S.R., J.J. Gard, L. Carvajal-Huerta, J.C. Ruiz-Cabezas, G. Thiene, and J.E. Saffitz. 2004. Structural and molecular pathology of the heart in Carvajal syndrome. Cardiovasc. Pathol. 13:26-32. http://dx.doi.org/ 10.1016/S1054-8807(03)00107-8
38. Kapplinger, J.D., A.P. Landstrom, B.A. Salisbury, T.E. Callis, G.D. Pollevick, D.J. Tester, M.G. Cox, Z. Bhuiyan, H. Bikker, A.C. Wiesfeld, et al. 2011. Distinguishing arrhythmogenic right ventricular cardiomyopathy/ dysplasia-associated mutations from background genetic noise. J. Am. Coll. Cardiol. 57:2317-2327. http://dx.doi.org/10.1016/j.jacc.2010.12.036
39. Klessner, J.L., B.V. Desai, E.V. Amargo, S. Getsios, and K.J. Green. 2009. EGFR and ADAMs cooperate to regulate shedding and endocytic trafficking of the desmosomal cadherin desmoglein 2. Mol. Biol. Cell. 20:328-337. http://dx.doi.org/10.1091/mbc.E08-04-0356
40. Kodama, A., I. Karakesisoglou, E. Wong, A. Vaezi, and E. Fuchs. 2003. ACF7: an essential integrator of microtubule dynamics. Cell. 115:343-354. http://dx.doi.org/10.1016/S0092-8674(03)00813-4
41. Komarova, Y., C.O. De Groot, I. Grigoriev, S.M. Gouveia, E.L. Munteanu, J.M. Schober, S. Honnappa, R.M. Buey, C.C. Hoogenraad, M. Dogterom, et al. 2009. Mammalian end binding proteins control persistent microtubule growth. J. Cell Biol. 184:691-706. http://dx.doi.org/10.1083/jcb.200807179
42. Kowalczyk, A.P., E.A. Bornslaeger, J.E. Borgwardt, H.L. Palka, A.S. Dhaliwal, C.M. Corcoran, M.F. Denning, and K.J. Green. 1997. The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes. J. Cell Biol. 139:773-784. http:// dx.doi.org/10.1083/jcb.139.3.773
43. Kowalczyk, A.P., M. Hatzfeld, E.A. Bornslaeger, D.S. Kopp, J.E. Borgwardt, C.M. Corcoran, A. Settler, and K.J. Green. 1999. The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes. Implications for cutaneous disease. J. Biol. Chem. 274:18145- 18148. http://dx.doi.org/10.1074/jbc.274.26.18145
44. Laird, D.W. 2006. Life cycle of connexins in health and disease. Biochem. J. 394:527-543. http://dx.doi.org/10.1042/BJ20051922
45. Lansbergen, G., and A. Akhmanova. 2006. Microtubule plus end: a hub of cellular activities. Traffic. 7:499-507. http://dx.doi.org/10.1111/j.1600-0854.2006.00400.x
46. Lauf, U., B.N. Giepmans, P. Lopez, S. Braconnot, S.C. Chen, and M.M. Falk. 2002. Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells. Proc. Natl. Acad. Sci. USA. 99:10446-10451. http://dx.doi.org/10.1073/pnas.162055899
47. Lechler, T., and E. Fuchs. 2007. Desmoplakin: an unexpected regulator of microtubule organization in the epidermis. J. Cell Biol. 176:147-154. http://dx.doi.org/10.1083/jcb.200609109
48. Leung, C.L., K.J. Green, and R.K. Liem. 2002. Plakins: a family of versatile cytolinker proteins. Trends Cell Biol. 12:37-45. http://dx.doi.org/10.1016/S0962-8924(01)02180-8
49. Ligon, L.A., and E.L. Holzbaur. 2007. Microtubules tethered at epithelial cell junctions by dynein facilitate efficient junction assembly. Traffic. 8:808- 819. http://dx.doi.org/10.1111/j.1600-0854.2007.00574.x
50. Lyon, R.C., V. Mezzano, A.T. Wright, E. Pfeiffer, J. Chuang, K. Banares, A. Castaneda, K. Ouyang, L. Cui, R. Contu, et al. 2014. Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model. Hum. Mol. Genet. 23:1134-1150. http://dx.doi.org/10.1093/hmg/ddt508
51. Meyers, C., and L.A. Laimins. 1994. In vitro systems for the study and propagation of human papillomaviruses. Curr. Top. Microbiol. Immunol. 186:199-215.
52. Morrison, E.E. 2007. Action and interactions at microtubule ends. Cell. Mol. Life Sci. 64:307-317. http://dx.doi.org/10.1007/s00018-007-6360-3
53. Musil, L.S., and D.A. Goodenough. 1991. Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. J. Cell Biol. 115:1357-1374. http://dx.doi.org/ 10.1083/jcb.115.5.1357
54. Nekrasova, O.E., E.V. Amargo, W.O. Smith, J. Chen, G.E. Kreitzer, and K.J. Green. 2011. Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes. J. Cell Biol. 195:1185-1203. http://dx.doi.org/ 10.1083/jcb.201106057
55. Noorman, M., M.A. van der Heyden, T.A. van Veen, M.G. Cox, R.N. Hauer, J.M. de Bakker, and H.V. van Rijen. 2009. Cardiac cell-cell junctions in health and disease: Electrical versus mechanical coupling. J. Mol. Cell. Cardiol. 47:23-31. http://dx.doi.org/10.1016/j.yjmcc.2009.03.016
56. Saffitz, J.E. 2006. Adhesion molecules: why they are important to the electrophysiologist. J. Cardiovasc. Electrophysiol. 17:225-229. http://dx.doi.org/10.1111/j.1540-8167.2006.00365.x
57. Shahbazi, M.N., D. Megias, C. Epifano, A. Akhmanova, G.G. Gundersen, E. Fuchs, and M. Perez-Moreno. 2013. CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions. J. Cell Biol. 203:1043-1061. http://dx.doi.org/10.1083/jcb.201306019
58. Shaw, R.M., A.J. Fay, M.A. Puthenveedu, M. von Zastrow, Y.N. Jan, and L.Y. Jan. 2007. Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions. Cell. 128:547-560. http://dx.doi.org/10.1016/j.cell.2006.12.037
59. Shtutman, M., A. Chausovsky, M. Prager-Khoutorsky, N. Schiefermeier, S. Boguslavsky, Z. Kam, E. Fuchs, B. Geiger, G.G. Borisy, and A.D. Bershadsky. 2008. Signaling function of ?-catenin in microtubule regulation. Cell Cycle. 7:2377-2383. http://dx.doi.org/10.4161/cc.6362
60. Simpson, C.L., D.M. Patel, and K.J. Green. 2011. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat. Rev. Mol. Cell Biol. 12:565-580. http://dx.doi.org/10.1038/nrm3175
61. Skube, S.B., J.M. Chaverri, and H.V. Goodson. 2010. Effect of GFP tags on the localization of EB1 and EB1 fragments in vivo. Cytoskeleton (Hoboken). 67:1-12. http://dx.doi.org/10.1002/cm.20409
62. Slep, K.C., S.L. Rogers, S.L. Elliott, H. Ohkura, P.A. Kolodziej, and R.D. Vale. 2005. Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end. J. Cell Biol. 168:587-598. http://dx.doi.org/10.1083/jcb.200410114
63. Smith, E.A., and E. Fuchs. 1998. Defining the interactions between intermediate filaments and desmosomes. J. Cell Biol. 141:1229-1241. http://dx.doi.org/10.1083/jcb.141.5.1229
64. So¨derberg, O., M. Gullberg, M. Jarvius, K. Ridderstra˚le, K.J. Leuchowius, J. Jarvius, K. Wester, P. Hydbring, F. Bahram, L.G. Larsson, and U. Landegren. 2006. Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat. Methods. 3:995-1000. http://dx.doi.org/10.1038/nmeth947
65. Solan, J.L., and P.D. Lampe. 2009. Connexin43 phosphorylation: structural changes and biological effects. Biochem. J. 419:261-272. http://dx.doi.org/10.1042/BJ20082319
66. Stappenbeck, T.S., E.A. Bornslaeger, C.M. Corcoran, H.H. Luu, M.L. Virata, and K.J. Green. 1993. Functional analysis of desmoplakin domains: specification of the interaction with keratin versus vimentin intermediate filament networks. J. Cell Biol. 123:691-705. http://dx.doi.org/10.1083/jcb.123.3.691
67. Su, L.K., M. Burrell, D.E. Hill, J. Gyuris, R. Brent, R. Wiltshire, J. Trent, B. Vogelstein, and K.W. Kinzler. 1995. APC binds to the novel protein EB1. Cancer Res. 55:2972-2977.
68. Subramanian, A., A. Prokop, M. Yamamoto, K. Sugimura, T. Uemura, J. Betschinger, J.A. Knoblich, and T. Volk. 2003. Shortstop recruits EB1/APC1 and promotes microtubule assembly at the muscle-tendon junction. Curr. Biol. 13:1086-1095. http://dx.doi.org/10.1016/S0960-9822(03)00416-0
69. Sumigray, K.D., H. Chen, and T. Lechler. 2011. Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. J. Cell Biol. 194:631-642. http://dx.doi.org/10.1083/jcb.201104009
70. Sumigray, K., K. Zhou, and T. Lechler. 2014. Cell-cell adhesions and cell contractility are upregulated upon desmosome disruption. PLoS ONE. 9:e101824. http://dx.doi.org/10.1371/journal.pone.0101824
71. Sun, D., C.L. Leung, and R.K. Liem. 2001. Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins. J. Cell Sci. 114:161-172.
72. Suozzi, K.C., X. Wu, and E. Fuchs. 2012. Spectraplakins: master orchestrators of cytoskeletal dynamics. J. Cell Biol. 197:465-475. http://dx.doi.org/10.1083/jcb.201112034
73. Tirnauer, J.S., S. Grego, E.D. Salmon, and T.J. Mitchison. 2002. EB1-microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules. Mol. Biol. Cell. 13:3614-3626. http://dx.doi.org/10.1091/mbc.02-04-0210
74. Vasioukhin, V., E. Bowers, C. Bauer, L. Degenstein, and E. Fuchs. 2001. Desmoplakin is essential in epidermal sheet formation. Nat. Cell Biol. 3:1076-1085. http://dx.doi.org/10.1038/ncb1201-1076
75. Vaughan, K.T. 2005. TIP maker and TIP marker; EB1 as a master controller of microtubule plus ends. J. Cell Biol. 171:197-200. http://dx.doi.org/ 10.1083/jcb.200509150
76. Wacker, I.U., J.E. Rickard, J.R. De Mey, and T.E. Kreis. 1992. Accumulation of a microtubule-binding protein, pp170, at desmosomal plaques. J. Cell Biol. 117:813-824. http://dx.doi.org/10.1083/jcb.117.4.813
77. Whittock, N.V., H. Wan, S.M. Morley, M.C. Garzon, L. Kristal, P. Hyde, W.H. McLean, L. Pulkkinen, J. Uitto, A.M. Christiano, et al. 2002. Compound heterozygosity for non-sense and mis-sense mutations in desmoplakinunderlies skin fragility/woolly hair syndrome. J. Invest. Dermatol. 118: 232-238. http://dx.doi.org/10.1046/j.0022-202x.2001.01664.x
78. Xu, T., Z. Yang, M. Vatta, A. Rampazzo, G. Beffagna, K. Pilichou, S.E. Scherer, J. Saffitz, J. Kravitz, W. Zareba, et al. Multidisciplinary Study of Right Ventricular Dysplasia Investigators. 2010. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J. Am. Coll. Cardiol. 55:587-597. (published erratum in J. Am. Coll. Cardiol. 2010. 55:1401) http://dx.doi.org/10.1016/j.jacc.2009.11.020
79. Yang, Y., C. Bauer, G. Strasser, R. Wollman, J.P. Julien, and E. Fuchs. 1999. Integrators of the cytoskeleton that stabilize microtubules. Cell. 98:229- 238. http://dx.doi.org/10.1016/S0092-8674(00)81017-X
80. Yang, Z., N.E. Bowles, S.E. Scherer, M.D. Taylor, D.L. Kearney, S. Ge, V.V. Nadvoretskiy, G. DeFreitas, B. Carabello, L.I. Brandon, et al. 2006. Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ. Res. 99:646- 655. http://dx.doi.org/10.1161/01.RES.0000241482.19382.c6
81. Yin, T., S. Getsios, R. Caldelari, A.P. Kowalczyk, E.J. Mu¨ller, J.C. Jones, and K.J. Green. 2005. Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA. 102:5420-5425. http://dx.doi.org/10.1073/pnas.0501676102
82. Zhang, Q., C. Deng, F. Rao, R.M. Modi, J. Zhu, X. Liu, L. Mai, H. Tan, X. Yu, Q. Lin, et al. 2013. Silencing of desmoplakin decreases connexin43/ Nav1.5 expression and sodium current in HL-1 cardiomyocytes. Mol. Med. Rep. 8:780-786.
83. Zhu, Z.C., K.K. Gupta, A.R. Slabbekoorn, B.A. Paulson, E.S. Folker, and H.V. Goodson. 2009. Interactions between EB1 and microtubules: dramatic effect of affinity tags and evidence for cooperative behavior. J. Biol. Chem. 284:32651-32661. http://dx.doi.org/10.1074/jbc.M109.013466