Hsp90-Associated Immunophilin Homolog Cpr7 Is Required for the Mitotic Stability of [URE3] Prion in

English version České info

Studies on yeast prions have provided insight into the role of various cellular factors involved in amyloid based disorders. Among the various cellular components the chaperone network has emerged as a crucial regulator of formation and propagation of yeast prions. The chaperone machinery primarily consists of Hsp70 and Hsp90 families of proteins, whose activity is further modulated by multiple co-chaperones. Though it is known that Hsp70s and its co-factors influence prion strength and stability, the role of Hsp90 chaperone machinery in yeast prion propagation is not clear. Here we examine the role of Hsp90 chaperones and show that the C-terminal MEEVD motif on Hsp90, which is required for interaction with tetratricopeptide repeat domain containing co-chaperones, is crucial for propagation of the yeast prion [URE3]. Further study revealed a novel role of the Hsp90 co-chaperone Cpr7 in the propagation of infectious amyloid and thus broadens our understanding about the cellular role of immunophilins.

Vyšlo v časopise: Hsp90-Associated Immunophilin Homolog Cpr7 Is Required for the Mitotic Stability of [URE3] Prion in. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005567
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005567

Souhrn

Zdroje

1. Wickner RB (1994) [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 264 : 566–569. 7909170

2. Derkatch IL, Bradley ME, Zhou P, Chernoff YO, Liebman SW (1997) Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae. Genetics 147 : 507–519. 9335589

3. Liebman SW, Chernoff YO (2012) Prions in yeast. Genetics 191 : 1041–1072. doi: 10.1534/genetics.111.137760 22879407

4. Klucken J, Shin Y, Masliah E, Hyman BT, McLean PJ (2004) Hsp70 Reduces alpha-Synuclein Aggregation and Toxicity. J Biol Chem 279 : 25497–25502. 15044495

5. Flower TR, Chesnokova LS, Froelich CA, Dixon C, Witt SN (2005) Heat shock prevents alpha-synuclein-induced apoptosis in a yeast model of Parkinson's disease. J Mol Biol 351 : 1081–1100. 16051265

6. Coughlan CM, Brodsky JL (2005) Use of yeast as a model system to investigate protein conformational diseases. Mol Biotechnol 30 : 171–180. 15920289

7. Sharma D, Masison DC (2009) Hsp70 structure, function, regulation and influence on yeast prions. Protein Pept Lett 16 : 571–581. 19519514

8. Shorter J, Lindquist S (2008) Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. EMBO J 27 : 2712–2724. doi: 10.1038/emboj.2008.194 18833196

9. Reidy M, Masison DC (2011) Modulation and elimination of yeast prions by protein chaperones and co-chaperones. Prion 5 : 245–249. doi: 10.4161/pri.17749 22052352

10. Sadlish H, Rampelt H, Shorter J, Wegrzyn RD, Andreasson C, et al. (2008) Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by two discrete activities. PLoS One 3: e1763. doi: 10.1371/journal.pone.0001763 18335038

11. Newnam GP, Birchmore JL, Chernoff YO (2011) Destabilization and recovery of a yeast prion after mild heat shock. J Mol Biol 408 : 432–448. doi: 10.1016/j.jmb.2011.02.034 21392508

12. Rikhvanov EG, Romanova NV, Chernoff YO (2007) Chaperone effects on prion and nonprion aggregates. Prion 1 : 217–222. 19164915

13. Park YN, Zhao X, Yim YI, Todor H, Ellerbrock R, et al. (2014) Hsp104 overexpression cures Saccharomyces cerevisiae [PSI+] by causing dissolution of the prion seeds. Eukaryot Cell 13 : 635–647. doi: 10.1128/EC.00300-13 24632242

14. Moriyama H, Edskes HK, Wickner RB (2000) [URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p. Mol Cell Biol 20 : 8916–8922. 11073991

15. Chernoff YO, Lindquist SL, Ono B, Inge-Vechtomov SG, Liebman SW (1995) Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science 268 : 880–884. 7754373

16. Sharma D, Masison DC (2008) Functionally redundant isoforms of a yeast Hsp70 chaperone subfamily have different antiprion effects. Genetics 179 : 1301–1311. doi: 10.1534/genetics.108.089458 18562668

17. Kryndushkin D, Wickner RB (2007) Nucleotide exchange factors for Hsp70s are required for [URE3] prion propagation in Saccharomyces cerevisiae. Mol Biol Cell 18 : 2149–2154. 17392510

18. Sharma D, Stanley RF, Masison DC (2009) Curing of yeast [URE3] prion by the Hsp40 cochaperone Ydj1p is mediated by Hsp70. Genetics 181 : 129–137. doi: 10.1534/genetics.108.098699 19015537

19. Fan Q, Park KW, Du Z, Morano KA, Li L (2007) The role of Sse1 in the de novo formation and variant determination of the [PSI+] prion. Genetics 177 : 1583–1593. 18039878

20. Hines JK, Li X, Du Z, Higurashi T, Li L, et al. (2011) [SWI], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity. PLoS Genet 7: e1001309. doi: 10.1371/journal.pgen.1001309 21379326

21. Summers DW, Douglas PM, Cyr DM (2009) Prion propagation by Hsp40 molecular chaperones. Prion 3 : 59–64. 19535913

22. Douglas PM, Treusch S, Ren HY, Halfmann R, Duennwald ML, et al. (2008) Chaperone-dependent amyloid assembly protects cells from prion toxicity. Proc Natl Acad Sci U S A 105 : 7206–7211. doi: 10.1073/pnas.0802593105 18480252

23. Shorter J, Lindquist S (2004) Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304 : 1793–1797. 15155912

24. Picard D, Khursheed B, Garabedian MJ, Fortin MG, Lindquist S, et al. (1990) Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 348 : 166–168. 2234079

25. Ali A, Bharadwaj S, O'Carroll R, Ovsenek N (1998) HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes. Mol Cell Biol 18 : 4949–4960. 9710578

26. Leach MD, Budge S, Walker L, Munro C, Cowen LE, et al. (2012) Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast. PLoS Pathog 8: e1003069. doi: 10.1371/journal.ppat.1003069 23300438

27. Grandin N, Charbonneau M (2001) Hsp90 levels affect telomere length in yeast. Mol Genet Genomics 265 : 126–134. 11370858

28. Wang X, Venable J, LaPointe P, Hutt DM, Koulov AV, et al. (2006) Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 127 : 803–815. 17110338

29. McLaughlin SH, Ventouras LA, Lobbezoo B, Jackson SE (2004) Independent ATPase activity of Hsp90 subunits creates a flexible assembly platform. J Mol Biol 344 : 813–826. 15533447

30. Prodromou C, Panaretou B, Chohan S, Siligardi G, O'Brien R, et al. (2000) The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains. EMBO J 19 : 4383–4392. 10944121

31. Hainzl O, Lapina MC, Buchner J, Richter K (2009) The charged linker region is an important regulator of Hsp90 function. J Biol Chem 284 : 22559–22567. doi: 10.1074/jbc.M109.031658 19553666

32. Brinker A, Scheufler C, Von Der Mulbe F, Fleckenstein B, Herrmann C, et al. (2002) Ligand discrimination by TPR domains. Relevance and selectivity of EEVD-recognition in Hsp70 x Hop x Hsp90 complexes. J Biol Chem 277 : 19265–19275. 11877417

33. D'Andrea LD, Regan L (2003) TPR proteins: the versatile helix. Trends Biochem Sci 28 : 655–662. 14659697

34. Zuehlke AD, Johnson JL (2012) Chaperoning the chaperone: a role for the co-chaperone Cpr7 in modulating Hsp90 function in Saccharomyces cerevisiae. Genetics 191 : 805–814. doi: 10.1534/genetics.112.140319 22505624

35. Duina AA, Marsh JA, Kurtz RB, Chang HC, Lindquist S, et al. (1998) The peptidyl-prolyl isomerase domain of the CyP-40 cyclophilin homolog Cpr7 is not required to support growth or glucocorticoid receptor activity in Saccharomyces cerevisiae. J Biol Chem 273 : 10819–10822. 9556552

36. Giustiniani J, Chambraud B, Sardin E, Dounane O, Guillemeau K, et al. (2014) Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy. Proc Natl Acad Sci U S A 111 : 4584–4589. doi: 10.1073/pnas.1402645111 24623856

37. Blair LJ, Baker JD, Sabbagh JJ, Dickey CA (2015) The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization, amyloid processing, and Alzheimer's disease. J Neurochem 133 : 1–13. doi: 10.1111/jnc.13033 25628064

38. Cintron NS, Toft D (2006) Defining the requirements for Hsp40 and Hsp70 in the Hsp90 chaperone pathway. J Biol Chem 281 : 26235–26244. 16854979

39. Song Y, Masison DC (2005) Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1). J Biol Chem 280 : 34178–34185. 16100115

40. Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, et al. (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440 : 1013–1017. 16625188

41. Richter K, Walter S, Buchner J (2004) The Co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle. J Mol Biol 342 : 1403–1413. 15364569

42. Panaretou B, Siligardi G, Meyer P, Maloney A, Sullivan JK, et al. (2002) Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol Cell 10 : 1307–1318. 12504007

43. Park KW, Hahn JS, Fan Q, Thiele DJ, Li L (2006) De novo appearance and "strain" formation of yeast prion [PSI+] are regulated by the heat-shock transcription factor. Genetics 173 : 35–47. 16452152

44. Reidy M, Masison DC (2010) Sti1 regulation of Hsp70 and Hsp90 is critical for curing of Saccharomyces cerevisiae [PSI+] prions by Hsp104. Mol Cell Biol 30 : 3542–3552. doi: 10.1128/MCB.01292-09 20479121

45. Moosavi B, Wongwigkarn J, Tuite MF (2010) Hsp70/Hsp90 co-chaperones are required for efficient Hsp104-mediated elimination of the yeast [PSI(+)] prion but not for prion propagation. Yeast 27 : 167–179. doi: 10.1002/yea.1742 20014008

46. Lancaster DL, Dobson CM, Rachubinski RA (2013) Chaperone proteins select and maintain [PIN+] prion conformations in Saccharomyces cerevisiae. J Biol Chem 288 : 1266–1276. doi: 10.1074/jbc.M112.377564 23148221

47. Kiktev DA, Patterson JC, Muller S, Bariar B, Pan T, et al. (2012) Regulation of chaperone effects on a yeast prion by cochaperone Sgt2. Mol Cell Biol 32 : 4960–4970. doi: 10.1128/MCB.00875-12 23045389

48. Schulte TW, Neckers LM (1998) The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother Pharmacol 42 : 273–279. 9744771

49. Krishnamoorthy GP, Guida T, Alfano L, Avilla E, Santoro M, et al. (2013) Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation. J Biol Chem 288 : 17481–17494. doi: 10.1074/jbc.M112.439422 23629654

50. Jones G, Song Y, Chung S, Masison DC (2004) Propagation of Saccharomyces cerevisiae [PSI+] prion is impaired by factors that regulate Hsp70 substrate binding. Mol Cell Biol 24 : 3928–3937. 15082786

51. Tanaka M, Collins SR, Toyama BH, Weissman JS (2006) The physical basis of how prion conformations determine strain phenotypes. Nature 442 : 585–589. 16810177

52. Sharma D, Masison DC (2011) Single methyl group determines prion propagation and protein degradation activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and Ssa2p. Proc Natl Acad Sci U S A 108 : 13665–13670. doi: 10.1073/pnas.1107421108 21808014

53. Duina AA, Marsh JA, Gaber RF (1996) Identification of two CyP-40-like cyclophilins in Saccharomyces cerevisiae, one of which is required for normal growth. Yeast 12 : 943–952. 8873448

54. Mayr C, Richter K, Lilie H, Buchner J (2000) Cpr6 and Cpr7, two closely related Hsp90-associated immunophilins from Saccharomyces cerevisiae, differ in their functional properties. J Biol Chem 275 : 34140–34146. 10942767

55. Marsh JA, Kalton HM, Gaber RF (1998) Cns1 is an essential protein associated with the hsp90 chaperone complex in Saccharomyces cerevisiae that can restore cyclophilin 40-dependent functions in cpr7Delta cells. Mol Cell Biol 18 : 7353–7359. 9819422

56. Freeman BC, Toft DO, Morimoto RI (1996) Molecular chaperone machines: chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23. Science 274 : 1718–1720. 8939864

57. Giustiniani J, Guillemeau K, Dounane O, Sardin E, Huvent I, et al. (2015) The FK506-binding protein FKBP52 in vitro induces aggregation of truncated Tau forms with prion-like behavior. FASEB J.

58. Mackay RG, Helsen CW, Tkach JM, Glover JR (2008) The C-terminal extension of Saccharomyces cerevisiae Hsp104 plays a role in oligomer assembly. Biochemistry 47 : 1918–1927. doi: 10.1021/bi701714s 18197703

59. Zuehlke AD, Wren N, Tenge V, Johnson JL (2013) Interaction of heat shock protein 90 and the co-chaperone Cpr6 with Ura2, a bifunctional enzyme required for pyrimidine biosynthesis. J Biol Chem 288 : 27406–27414. doi: 10.1074/jbc.M113.504142 23926110

60. Hainzl O, Wegele H, Richter K, Buchner J (2004) Cns1 is an activator of the Ssa1 ATPase activity. J Biol Chem 279 : 23267–23273. 15044454

61. Wegele H, Haslbeck M, Reinstein J, Buchner J (2003) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278 : 25970–25976. 12716905

62. Dolinski KJ, Cardenas ME, Heitman J (1998) CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses cyclophilin 40 mutations and interacts with Hsp90. Mol Cell Biol 18 : 7344–7352. 9819421

63. Yang J, Roe SM, Cliff MJ, Williams MA, Ladbury JE, et al. (2005) Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. EMBO J 24 : 1–10. 15577939

64. Kumar N, Gaur D, Masison DC, Sharma D (2014) The BAG homology domain of Snl1 cures yeast prion [URE3] through regulation of Hsp70 chaperones. G3 (Bethesda) 4 : 461–470.