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EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for


Chlamydia trachomatis are major human pathogens causing ocular and sexually transmitted diseases with hundreds of millions of cases per year. Chlamydia replicate inside the host cell in a membrane bound vacuole called inclusion. The current concept on how Chlamydia communicates with the host cell during its replication is based on the identification of the host protein that interacts with Chlamydia. Here, we describe that C. trachomatis-serovar L2 and D use EphA2, a member of the largest class of human receptor tyrosine kinases, as an adherence and entry receptor that is endocytosed together with the bacteria. Cell surface EphA2 receptor is adopted by Chlamydia to function also at the inclusion to support growth and replication and to keep the infected cell in an apoptosis resistant state. Thus, we show that EphA2 is an undiscovered important surface and intracellular signaling receptor that is crucial for chlamydial infection and development.


Vyšlo v časopise: EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004846
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004846

Souhrn

Chlamydia trachomatis are major human pathogens causing ocular and sexually transmitted diseases with hundreds of millions of cases per year. Chlamydia replicate inside the host cell in a membrane bound vacuole called inclusion. The current concept on how Chlamydia communicates with the host cell during its replication is based on the identification of the host protein that interacts with Chlamydia. Here, we describe that C. trachomatis-serovar L2 and D use EphA2, a member of the largest class of human receptor tyrosine kinases, as an adherence and entry receptor that is endocytosed together with the bacteria. Cell surface EphA2 receptor is adopted by Chlamydia to function also at the inclusion to support growth and replication and to keep the infected cell in an apoptosis resistant state. Thus, we show that EphA2 is an undiscovered important surface and intracellular signaling receptor that is crucial for chlamydial infection and development.


Zdroje

1. Mabey DC, Solomon AW, Foster A (2003) Trachoma. Lancet 362: 223–229. 12885486

2. Wilkowska-Trojniel M, Zdrodowska-Stefanow B, Ostaszewska-Puchalska I, Zbucka M, Wolczynski S, et al. (2009) Chlamydia trachomatis urogenital infection in women with infertility. Adv Med Sci 54: 82–85. doi: 10.2478/v10039-009-0007-6 19731407

3. Clifton DR, Fields KA, Grieshaber SS, Dooley CA, Fischer ER, et al. (2004) A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin. Proc Natl Acad Sci U S A 101: 10166–10171. 15199184

4. Betts HJ, Wolf K, Fields KA (2009) Effector protein modulation of host cells: examples in the Chlamydia spp. arsenal. Curr Opin Microbiol 12: 81–87. doi: 10.1016/j.mib.2008.11.009 19138553

5. Damiani MT, Gambarte Tudela J, Capmany A (2014) Targeting eukaryotic Rab proteins: a smart strategy for chlamydial survival and replication. Cell Microbiol 16: 1329–1338. doi: 10.1111/cmi.12325 24948448

6. Davis CH, Raulston JE, Wyrick PB (2002) Protein disulfide isomerase, a component of the estrogen receptor complex, is associated with Chlamydia trachomatis serovar E attached to human endometrial epithelial cells. Infect Immun 70: 3413–3418. 12065480

7. Conant CG, Stephens RS (2007) Chlamydia attachment to mammalian cells requires protein disulfide isomerase. Cell Microbiol 9: 222–232. 16925789

8. Elwell CA, Ceesay A, Kim JH, Kalman D, Engel JN (2008) RNA interference screen identifies Abl kinase and PDGFR signaling in Chlamydia trachomatis entry. PLoS Pathog 4: e1000021. doi: 10.1371/journal.ppat.1000021 18369471

9. Kim JH, Jiang S, Elwell CA, Engel JN (2011) Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection. PLoS Pathog 7: e1002285. doi: 10.1371/journal.ppat.1002285 21998584

10. Molleken K, Becker E, Hegemann JH (2013) The Chlamydia pneumoniae invasin protein Pmp21 recruits the EGF receptor for host cell entry. PLoS Pathog 9: e1003325. doi: 10.1371/journal.ppat.1003325 23633955

11. Mital J, Hackstadt T (2011) Role for the SRC family kinase Fyn in sphingolipid acquisition by chlamydiae. Infect Immun 79: 4559–4568. doi: 10.1128/IAI.05692-11 21896774

12. Olive AJ, Haff MG, Emanuele MJ, Sack LM, Barker JR, et al. (2014) Chlamydia trachomatis-induced alterations in the host cell proteome are required for intracellular growth. Cell Host Microbe 15: 113–124. doi: 10.1016/j.chom.2013.12.009 24439903

13. Verbeke P, Welter-Stahl L, Ying S, Hansen J, Hacker G, et al. (2006) Recruitment of BAD by the Chlamydia trachomatis vacuole correlates with host-cell survival. PLoS Pathog 2: e45. 16710454

14. Rajalingam K, Sharma M, Lohmann C, Oswald M, Thieck O, et al. (2008) Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells. PLoS One 3: e3102. doi: 10.1371/journal.pone.0003102 18769617

15. Kullander K, Klein R (2002) Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3: 475–486. 12094214

16. Pasquale EB (2005) Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6: 462–475. 15928710

17. Pasquale EB (2008) Eph-ephrin bidirectional signaling in physiology and disease. Cell 133: 38–52. doi: 10.1016/j.cell.2008.03.011 18394988

18. Himanen JP, Goldgur Y, Miao H, Myshkin E, Guo H, et al. (2009) Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex. EMBO Rep 10: 722–728. doi: 10.1038/embor.2009.91 19525919

19. Pasquale EB (2010) Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 10: 165–180. doi: 10.1038/nrc2806 20179713

20. Surawska H, Ma PC, Salgia R (2004) The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev 15: 419–433. 15561600

21. Al-Younes HM, Rudel T, Meyer TF (1999) Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells. Cell Microbiol 1: 237–247. 11207556

22. Albrecht M, Sharma CM, Reinhardt R, Vogel J, Rudel T (2010) Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome. Nucleic Acids Res 38: 868–877. doi: 10.1093/nar/gkp1032 19923228

23. Wang Y, Kahane S, Cutcliffe LT, Skilton RJ, Lambden PR, et al. (2011) Development of a transformation system for Chlamydia trachomatis: restoration of glycogen biosynthesis by acquisition of a plasmid shuttle vector. PLoS Pathog 7: e1002258. doi: 10.1371/journal.ppat.1002258 21966270

24. Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, et al. (2010) COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468: 968–972. doi: 10.1038/nature09627 21107320

25. Ueki K, Fruman DA, Yballe CM, Fasshauer M, Klein J, et al. (2003) Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling. J Biol Chem 278: 48453–48466. 14504291

26. Abromaitis S, Stephens RS (2009) Attachment and entry of Chlamydia have distinct requirements for host protein disulfide isomerase. PLoS Pathog 5: e1000357. doi: 10.1371/journal.ppat.1000357 19343202

27. Hahn AS, Kaufmann JK, Wies E, Naschberger E, Panteleev-Ivlev J, et al. (2012) The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus. Nat Med 18: 961–966. doi: 10.1038/nm.2805 22635007

28. Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141: 1117–1134. doi: 10.1016/j.cell.2010.06.011 20602996

29. Chang Q, Jorgensen C, Pawson T, Hedley DW (2008) Effects of dasatinib on EphA2 receptor tyrosine kinase activity and downstream signalling in pancreatic cancer. Br J Cancer 99: 1074–1082. doi: 10.1038/sj.bjc.6604676 18797457

30. Lupberger J, Zeisel MB, Xiao F, Thumann C, Fofana I, et al. (2011) EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med 17: 589–595. doi: 10.1038/nm.2341 21516087

31. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, et al. (2004) Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 47: 6658–6661. 15615512

32. Melnick JS, Janes J, Kim S, Chang JY, Sipes DG, et al. (2006) An efficient rapid system for profiling the cellular activities of molecular libraries. Proc Natl Acad Sci U S A 103: 3153–3158. 16492761

33. Walker-Daniels J, Riese DJ 2nd, Kinch MS (2002) c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. Mol Cancer Res 1: 79–87. 12496371

34. Fang WB, Brantley-Sieders DM, Hwang Y, Ham AJ, Chen J (2008) Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase. J Biol Chem 283: 16017–16026. doi: 10.1074/jbc.M709934200 18387945

35. Chakraborty S, Veettil MV, Bottero V, Chandran B (2012) Kaposi's sarcoma-associated herpesvirus interacts with EphrinA2 receptor to amplify signaling essential for productive infection. Proc Natl Acad Sci U S A 109: E1163–1172. doi: 10.1073/pnas.1119592109 22509030

36. Hess S, Peters J, Bartling G, Rheinheimer C, Hegde P, et al. (2003) More than just innate immunity: comparative analysis of Chlamydophila pneumoniae and Chlamydia trachomatis effects on host-cell gene regulation. Cell Microbiol 5: 785–795. 14531894

37. Taddei ML, Parri M, Angelucci A, Onnis B, Bianchini F, et al. (2009) Kinase-dependent and-independent roles of EphA2 in the regulation of prostate cancer invasion and metastasis. Am J Pathol 174: 1492–1503. doi: 10.2353/ajpath.2009.080473 19264906

38. Fan T, Lu H, Hu H, Shi L, McClarty GA, et al. (1998) Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med 187: 487–496. 9463399

39. Mohammed KA, Wang X, Goldberg EP, Antony VB, Nasreen N (2011) Silencing receptor EphA2 induces apoptosis and attenuates tumor growth in malignant mesothelioma. Am J Cancer Res 1: 419–431. 21968554

40. Zhou Z, Yuan X, Li Z, Tu H, Li D, et al. (2008) RNA interference targeting EphA2 inhibits proliferation, induces apoptosis, and cooperates with cytotoxic drugs in human glioma cells. Surg Neurol 70: 562–568; discussion 568–569. doi: 10.1016/j.surneu.2008.04.031 18614215

41. Hirai H, Maru Y, Hagiwara K, Nishida J, Takaku F (1987) A novel putative tyrosine kinase receptor encoded by the eph gene. Science 238: 1717–1720. 2825356

42. Boissier P, Chen J, Huynh-Do U (2013) EphA2 signaling following endocytosis: role of Tiam1. Traffic 14: 1255–1271. doi: 10.1111/tra.12123 24112471

43. Miura K, Nam JM, Kojima C, Mochizuki N, Sabe H (2009) EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts. Mol Biol Cell 20: 1949–1959. doi: 10.1091/mbc.E08-06-0549 19193766

44. Kaplan N, Fatima A, Peng H, Bryar PJ, Lavker RM, et al. (2012) EphA2/Ephrin-A1 signaling complexes restrict corneal epithelial cell migration. Invest Ophthalmol Vis Sci 53: 936–945. doi: 10.1167/iovs.11-8685 22247486

45. Patel AL, Chen X, Wood ST, Stuart ES, Arcaro KF, et al. (2014) Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development. BMC Microbiol 14: 277. 25471819

46. Hybiske K, Stephens RS (2007) Mechanisms of Chlamydia trachomatis entry into nonphagocytic cells. Infect Immun 75: 3925–3934. 17502389

47. Pitulescu ME, Adams RH (2010) Eph/ephrin molecules—a hub for signaling and endocytosis. Genes Dev 24: 2480–2492. doi: 10.1101/gad.1973910 21078817

48. Lin YG, Han LY, Kamat AA, Merritt WM, Landen CN, et al. (2007) EphA2 overexpression is associated with angiogenesis in ovarian cancer. Cancer 109: 332–340. 17154180

49. Bast RC Jr., Hennessy B, Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 9: 415–428. doi: 10.1038/nrc2644 19461667

50. Shaw JL, Wills GS, Lee KF, Horner PJ, McClure MO, et al. (2011) Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFkappaB activation resulting in a microenvironment predisposed to ectopic pregnancy. Am J Pathol 178: 253–260. doi: 10.1016/j.ajpath.2010.11.019 21224062

51. Jerchel S, Knebel G, Konig P, Bohlmann MK, Rupp J (2012) A human fallopian tube model for investigation of C. trachomatis infections. J Vis Exp.

52. Wong A, Maclean AB, Furrows SJ, Ridgway GL, Hardiman PJ, et al. (2007) Could epithelial ovarian cancer be associated with chlamydial infection? Eur J Gynaecol Oncol 28: 117–120. 17479672

53. Carvalho JP, Carvalho FM (2008) Is Chlamydia-infected tubal fimbria the origin of ovarian cancer? Med Hypotheses 71: 690–693. doi: 10.1016/j.mehy.2008.06.028 18703287

54. Morre SA, Sillekens PT, Jacobs MV, de Blok S, Ossewaarde JM, et al. (1998) Monitoring of Chlamydia trachomatis infections after antibiotic treatment using RNA detection by nucleic acid sequence based amplification. Mol Pathol 51: 149–154. 9850338

55. Morrison RP (2003) New insights into a persistent problem—chlamydial infections. J Clin Invest 111: 1647–1649. 12782667

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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