A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane

1. Buchberger A, Bukau B, Sommer T (2010) Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol Cell 40: 238–252. doi: 10.1016/j.molcel.2010.10.001 20965419

2. Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475: 324–332. doi: 10.1038/nature10317 21776078

3. Saibil H (2013) Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Mol Cell Biol 14: 630–642. doi: 10.1038/nrm3658 24026055

4. Hetz C, Chevet E, Harding HP (2013) Targeting the unfolded protein response in disease. Nat Rev Drug Discov 12: 703–719. doi: 10.1038/nrd3976 23989796

5. Sontag EM, Vonk WI, Frydman J (2014) Sorting out the trash: the spatial nature of eukaryotic protein quality control. Curr Opin Cell Biol 26: 139–146. doi: 10.1016/j.ceb.2013.12.006 24463332

6. Easton DP, Kaneko Y, Subjeck JR (2000) The hsp110 and Grp1 70 stress proteins: newly recognized relatives of the Hsp70s. Cell Stress Chaperones 5: 276–290. 11048651

7. Dragovic Z, Broadley SA, Shomura Y, Bracher A, Hartl FU (2006) Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s. EMBO J 25: 2519–2528. 16688212

8. Raviol H, Bukau B, Mayer MP (2006) Human and yeast Hsp110 chaperones exhibit functional differences. FEBS Lett 580: 168–174. 16364315

9. Polier S, Dragovic Z, Hartl FU, Bracher A (2008) Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding. Cell 133: 1068–1079. doi: 10.1016/j.cell.2008.05.022 18555782

10. Bracher A, Verghese J (2015) GrpE, Hsp110/Grp170, HspBP1/Sil1 and BAG Domain Proteins: Nucleotide Exchange Factors for Hsp70 Molecular Chaperones. Subcell Biochem 78: 1–33. doi: 10.1007/978-3-319-11731-7_1 25487014

11. Sakurai T, Kashida H, Hagiwara S, Nishida N, Watanabe T, et al. (2015) Heat Shock Protein A4 Controls Cell Migration and Gastric Ulcer Healing. Dig Dis Sci.

12. Makhnevych T, Wong P, Pogoutse O, Vizeacoumar FJ, Greenblatt JF, et al. (2012) Hsp110 is required for spindle length control. J Cell Biol 198: 623–636. doi: 10.1083/jcb.201111105 22908312

13. Yu N, Kakunda M, Pham V, Lill JR, Du P, et al. (2015) HSP105 Recruits PP2A to Dephosphorylate beta-Catenin. Mol Cell Biol.

14. Yamashita H, Kawamata J, Okawa K, Kanki R, Nakamizo T, et al. (2007) Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS. J Neurochem 102: 1497–1505. 17403032

15. Song Y, Nagy M, Ni W, Tyagi NK, Fenton WA, et al. (2013) Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm. Proc Natl Acad Sci U S A 110: 5428–5433. doi: 10.1073/pnas.1303279110 23509252

16. 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

17. Eroglu B, Moskophidis D, Mivechi NF (2010) Loss of Hsp110 leads to age-dependent tau hyperphosphorylation and early accumulation of insoluble amyloid beta. Mol Cell Biol 30: 4626–4643. doi: 10.1128/MCB.01493-09 20679486

18. Saxena A, Banasavadi-Siddegowda YK, Fan Y, Bhattacharya S, Roy G, et al. (2012) Human heat shock protein 105/110 kDa (Hsp105/110) regulates biogenesis and quality control of misfolded cystic fibrosis transmembrane conductance regulator at multiple levels. J Biol Chem 287: 19158–19170. doi: 10.1074/jbc.M111.297580 22505710

19. Muralidharan V, Oksman A, Pal P, Lindquist S, Goldberg DE (2012) Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers. Nat Commun 3: 1310. doi: 10.1038/ncomms2306 23250440

20. Kuo Y, Ren S, Lao U, Edgar BA, Wang T (2013) Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110. Cell Death Dis 4: e833. doi: 10.1038/cddis.2013.351 24091676

21. Kampinga HH, Craig EA (2010) The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 11: 579–592. doi: 10.1038/nrm2941 20651708

22. Oh HJ, Chen X, Subjeck JR (1997) Hsp110 protects heat-denatured proteins and confers cellular thermoresistance. J Biol Chem 272: 31636–31640. 9395504

23. Shorter J (2011) The mammalian disaggregase machinery: Hsp110 synergizes with Hsp70 and Hsp40 to catalyze protein disaggregation and reactivation in a cell-free system. PLoS One 6: e26319. doi: 10.1371/journal.pone.0026319 22022600

24. Rampelt H, Kirstein-Miles J, Nillegoda NB, Chi K, Scholz SR, et al. (2012) Metazoan Hsp70 machines use Hsp110 to power protein disaggregation. EMBO J 31: 4221–4235. doi: 10.1038/emboj.2012.264 22990239

25. Mattoo RU, Sharma SK, Priya S, Finka A, Goloubinoff P (2013) Hsp110 is a bona fide chaperone using ATP to unfold stable misfolded polypeptides and reciprocally collaborate with Hsp70 to solubilize protein aggregates. J Biol Chem 288: 21399–21411. doi: 10.1074/jbc.M113.479253 23737532

26. Pelkmans L, Kartenbeck J, Helenius A (2001) Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 3: 473–483. 11331875

27. Bernacchi S, Mueller G, Langowski J, Waldeck W (2004) Characterization of simian virus 40 on its infectious entry pathway in cells using fluorescence correlation spectroscopy. Biochem Soc Trans 32: 746–749. 15494004

28. Spooner RA, Smith DC, Easton AJ, Roberts LM, Lord JM (2006) Retrograde transport pathways utilised by viruses and protein toxins. Virol J 3: 26. 16603059

29. Tsai B, Qian M (2010) Cellular entry of polyomaviruses. Curr Top Microbiol Immunol 343: 177–194. doi: 10.1007/82_2010_38 20373089

30. Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, et al. (1991) Structure of simian virus 40 at 3.8-A resolution. Nature 354: 278–284. 1659663

31. Stehle T, Gamblin SJ, Yan Y, Harrison SC (1996) The structure of simian virus 40 refined at 3.1 A resolution. Structure 4: 165–182. 8805523

32. Kartenbeck J, Stukenbrok H, Helenius A (1989) Endocytosis of simian virus 40 into the endoplasmic reticulum. J Cell Biol 109: 2721–2729. 2556405

33. Qian M, Cai D, Verhey KJ, Tsai B (2009) A lipid receptor sorts polyomavirus from the endolysosome to the endoplasmic reticulum to cause infection. PLoS Pathog 5: e1000465. doi: 10.1371/journal.ppat.1000465 19503604

34. Engel S, Heger T, Mancini R, Herzog F, Kartenbeck J, et al. (2011) Role of endosomes in simian virus 40 entry and infection. J Virol 85: 4198–4211. doi: 10.1128/JVI.02179-10 21345959

35. Rainey-Barger EK, Magnuson B, Tsai B (2007) A chaperone-activated nonenveloped virus perforates the physiologically relevant endoplasmic reticulum membrane. J Virol 81: 12996–13004. 17881435

36. Schelhaas M, Malmstrom J, Pelkmans L, Haugstetter J, Ellgaard L, et al. (2007) Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells. Cell 131: 516–529. 17981119

37. Geiger R, Andritschke D, Friebe S, Herzog F, Luisoni S, et al. (2011) BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol. Nat Cell Biol 13: 1305–1314. doi: 10.1038/ncb2339 21947079

38. Goodwin EC, Lipovsky A, Inoue T, Magaldi TG, Edwards AP, et al. (2011) BiP and multiple DNAJ molecular chaperones in the endoplasmic reticulum are required for efficient simian virus 40 infection. MBio 2: e00101–00111. doi: 10.1128/mBio.00101-11 21673190

39. Inoue T, Tsai B (2011) A large and intact viral particle penetrates the endoplasmic reticulum membrane to reach the cytosol. PLoS Pathog 7: e1002037. doi: 10.1371/journal.ppat.1002037 21589906

40. Magnuson B, Rainey EK, Benjamin T, Baryshev M, Mkrtchian S, et al. (2005) ERp29 triggers a conformational change in polyomavirus to stimulate membrane binding. Mol Cell 20: 289–300. 16246730

41. Norkin LC, Anderson HA, Wolfrom SA, Oppenheim A (2002) Caveolar endocytosis of simian virus 40 is followed by brefeldin A-sensitive transport to the endoplasmic reticulum, where the virus disassembles. J Virol 76: 5156–5166. 11967331

42. Daniels R, Rusan NM, Wadsworth P, Hebert DN (2006) SV40 VP2 and VP3 insertion into ER membranes is controlled by the capsid protein VP1: implications for DNA translocation out of the ER. Mol Cell 24: 955–966. 17189196

43. Walczak CP, Ravindran MS, Inoue T, Tsai B (2014) A cytosolic chaperone complexes with dynamic membrane J-proteins and mobilizes a nonenveloped virus out of the endoplasmic reticulum. PLoS Pathog 10: e1004007. doi: 10.1371/journal.ppat.1004007 24675744

44. Sopha P, Kadokura H, Yamamoto YH, Takeuchi M, Saito M, et al. (2012) A novel mammalian ER-located J-protein, DNAJB14, can accelerate ERAD of misfolded membrane proteins. Cell Struct Funct 37: 177–187. 23018488

45. Abrams JL, Verghese J, Gibney PA, Morano KA (2014) Hierarchical functional specificity of cytosolic heat shock protein 70 (Hsp70) nucleotide exchange factors in yeast. J Biol Chem 289: 13155–13167. doi: 10.1074/jbc.M113.530014 24671421

46. Schuermann JP, Jiang J, Cuellar J, Llorca O, Wang L, et al. (2008) Structure of the Hsp110:Hsc70 nucleotide exchange machine. Mol Cell 31: 232–243. doi: 10.1016/j.molcel.2008.05.006 18550409

47. Weitzmann A, Baldes C, Dudek J, Zimmermann R (2007) The heat shock protein 70 molecular chaperone network in the pancreatic endoplasmic reticulum—a quantitative approach. FEBS J 274: 5175–5187. 17850331

48. Andreasson C, Rampelt H, Fiaux J, Druffel-Augustin S, Bukau B (2010) The endoplasmic reticulum Grp170 acts as a nucleotide exchange factor of Hsp70 via a mechanism similar to that of the cytosolic Hsp110. J Biol Chem 285: 12445–12453. doi: 10.1074/jbc.M109.096735 20177057

49. Hale SJ, Lovell SC, de Keyzer J, Stirling CJ (2010) Interactions between Kar2p and its nucleotide exchange factors Sil1p and Lhs1p are mechanistically distinct. J Biol Chem 285: 21600–21606. doi: 10.1074/jbc.M110.111211 20430899

50. de Keyzer J, Steel GJ, Hale SJ, Humphries D, Stirling CJ (2009) Nucleotide binding by Lhs1p is essential for its nucleotide exchange activity and for function in vivo. J Biol Chem 284: 31564–31571. doi: 10.1074/jbc.M109.055160 19759005

51. Inoue T, Tsai B (2015) A Nucleotide Exchange Factor Promotes ER-to-cytosol Membrane Penetration of the Non-enveloped Virus SV40. J Virol.

52. Wernick NL, De Luca H, Kam WR, Lencer WI (2010) N-terminal extension of the cholera toxin A1-chain causes rapid degradation after retrotranslocation from endoplasmic reticulum to cytosol. J Biol Chem 285: 6145–6152. doi: 10.1074/jbc.M109.062067 20056601

53. Walczak CP, Tsai B (2011) A PDI family network acts distinctly and coordinately with ERp29 to facilitate polyomavirus infection. J Virol 85: 2386–2396. doi: 10.1128/JVI.01855-10 21159867

54. Bagchi P, Walczak CP, Tsai B (2015) The ER membrane J protein C18 executes a distinct role in promoting SV40 membrane penetration. J Virol.

55. Chromy LR, Oltman A, Estes PA, Garcea RL (2006) Chaperone-mediated in vitro disassembly of polyoma- and papillomaviruses. J Virol 80: 5086–5091. 16641302

56. Mattoo RU, Goloubinoff P (2014) Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins. Cell Mol Life Sci 71: 3311–3325. doi: 10.1007/s00018-014-1627-y 24760129

57. Yam AY, Albanese V, Lin HT, Frydman J (2005) Hsp110 cooperates with different cytosolic HSP70 systems in a pathway for de novo folding. J Biol Chem 280: 41252–41261. 16219770

58. Olzmann JA, Kopito RR, Christianson JC (2013) The mammalian endoplasmic reticulum-associated degradation system. Cold Spring Harb Perspect Biol 5.

59. Brodsky JL (2012) Cleaning up: ER-associated degradation to the rescue. Cell 151: 1163–1167. doi: 10.1016/j.cell.2012.11.012 23217703

60. Houck SA, Ren HY, Madden VJ, Bonner JN, Conlin MP, et al. (2014) Quality control autophagy degrades soluble ERAD-resistant conformers of the misfolded membrane protein GnRHR. Mol Cell 54: 166–179. doi: 10.1016/j.molcel.2014.02.025 24685158

61. Grove DE, Fan CY, Ren HY, Cyr DM (2011) The endoplasmic reticulum-associated Hsp40 DNAJB12 and Hsc70 cooperate to facilitate RMA1 E3-dependent degradation of nascent CFTRDeltaF508. Mol Biol Cell 22: 301–314. doi: 10.1091/mbc.E10-09-0760 21148293

62. Yamamoto YH, Kimura T, Momohara S, Takeuchi M, Tani T, et al. (2010) A novel ER J-protein DNAJB12 accelerates ER-associated degradation of membrane proteins including CFTR. Cell Struct Funct 35: 107–116. 21150129

63. Hrizo SL, Gusarova V, Habiel DM, Goeckeler JL, Fisher EA, et al. (2007) The Hsp110 molecular chaperone stabilizes apolipoprotein B from endoplasmic reticulum-associated degradation (ERAD). J Biol Chem 282: 32665–32675. 17823116

64. Hazes B, Read RJ (1997) Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry 36: 11051–11054. 9333321

65. Rodighiero C, Tsai B, Rapoport TA, Lencer WI (2002) Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation. EMBO Rep 3: 1222–1227. 12446567

66. Ye Y, Meyer HH, Rapoport TA (2001) The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature 414: 652–656. 11740563

67. Kothe M, Ye Y, Wagner JS, De Luca HE, Kern E, et al. (2005) Role of p97 AAA-ATPase in the retrotranslocation of the cholera toxin A1 chain, a non-ubiquitinated substrate. J Biol Chem 280: 28127–28132. 15932873

68. Moore P, He K, Tsai B (2013) Establishment of an in vitro transport assay that reveals mechanistic differences in cytosolic events controlling cholera toxin and T-cell receptor alpha retro-translocation. Plos One 8: e75801. doi: 10.1371/journal.pone.0075801 24146777

69. Kuksin D, Norkin LC (2012) Disassembly of simian virus 40 during passage through the endoplasmic reticulum and in the cytoplasm. J Virol 86: 1555–1562. doi: 10.1128/JVI.05753-11 22090139

70. Ungewickell E, Ungewickell H, Holstein SE, Lindner R, Prasad K, et al. (1995) Role of auxilin in uncoating clathrin-coated vesicles. Nature 378: 632–635. 8524399

71. Prasad K, Barouch W, Greene L, Eisenberg E (1993) A protein cofactor is required for uncoating of clathrin baskets by uncoating ATPase. J Biol Chem 268: 23758–23761. 8226905

72. Heuser JE, Anderson RG (1989) Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. J Cell Biol 108: 389–400. 2563728

73. Wickner W, Schekman R (2005) Protein translocation across biological membranes. Science 310: 1452–1456. 16322447

74. Matlack KE, Misselwitz B, Plath K, Rapoport TA (1999) BiP acts as a molecular ratchet during posttranslational transport of prepro-alpha factor across the ER membrane. Cell 97: 553–564. 10367885

75. Tanimura S, Hirano AI, Hashizume J, Yasunaga M, Kawabata T, et al. (2007) Anticancer drugs up-regulate HspBP1 and thereby antagonize the prosurvival function of Hsp70 in tumor cells. J Biol Chem 282: 35430–35439. 17855353

76. Uemura A, Oku M, Mori K, Yoshida H (2009) Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the mammalian unfolded protein response. J Cell Sci 122: 2877–2886. doi: 10.1242/jcs.040584 19622636

77. Chung KT, Shen Y, Hendershot LM (2002) BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP. J Biol Chem 277: 47557–47563. 12356756

78. Steel GJ, Fullerton DM, Tyson JR, Stirling CJ (2004) Coordinated activation of Hsp70 chaperones. Science 303: 98–101. 14704430