Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis

English version

Autoři: Joao Vasco Ferreira ^aff001; Ana Rosa Soares ^aff001; José S. Ramalho ^aff001; Teresa Ribeiro-Rodrigues ^aff002; Catarina Máximo ^aff001; Mónica Zuzarte ^aff002; Henrique Girão ^aff002; Paulo Pereira ^aff001
Působiště autorů: CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal ^aff001; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Coimbra, Portugal ^aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0223790

Souhrn

Deregulation of proteostasis is a main feature of many age-related diseases, often leading to the accumulation of toxic oligomers and insoluble protein aggregates that accumulate intracellularly or in the extracellular space. To understand the mechanisms whereby toxic or otherwise unwanted proteins are secreted to the extracellular space, we inactivated the quality-control and proteostasis regulator ubiquitin ligase STUB1/CHIP. Data indicated that STUB1 deficiency leads both to the intracellular accumulation of protein aggregates and to an increase in the secretion of small extracellular vesicles (sEVs), including exosomes. Secreted sEVs are enriched in ubiquitinated and/or undegraded proteins and protein oligomers. Data also indicates that oxidative stress induces an increase in the release of sEVs in cells depleted from STUB1. Overall, the results presented here suggest that cells use exosomes to dispose of damaged and/or undegraded proteins as a means to reduce intracellular accumulation of proteotoxic material.

Klíčová slova:

Membrane proteins – Vesicles – Oligomers – Oxidative stress – Secretion – Protein secretion – Goats – Exosomes

Zdroje

1. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–217. doi: 10.1016/j.cell.2013.05.039 23746838

2. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem. 2009;78:959–91. doi: 10.1146/annurev.biochem.052308.114844 19298183.

3. Tanaka K, Matsuda N. Proteostasis and neurodegeneration: the roles of proteasomal degradation and autophagy. Biochim Biophys Acta. 2014;1843(1):197–204. doi: 10.1016/j.bbamcr.2013.03.012 23523933.

4. Schmidt M, Finley D. Regulation of proteasome activity in health and disease. Biochim Biophys Acta. 2014;1843(1):13–25. doi: 10.1016/j.bbamcr.2013.08.012 23994620

5. Calderwood SK, Murshid A, Prince T. The shock of aging: molecular chaperones and the heat shock response in longevity and aging—a mini-review. Gerontology. 2009;55(5):550–8. doi: 10.1159/000225957 19546513

6. Bosco DA, LaVoie MJ, Petsko GA, Ringe D. Proteostasis and movement disorders: Parkinson’s disease and amyotrophic lateral sclerosis. Cold Spring Harb Perspect Biol. 2011;3(10):a007500. doi: 10.1101/cshperspect.a007500 21844169

7. Abdelfattah NS, Zhang H, Boyer DS, Rosenfeld PJ, Feuer WJ, Gregori G, et al. Drusen Volume as a Predictor of Disease Progression in Patients With Late Age-Related Macular Degeneration in the Fellow Eye. Invest Ophthalmol Vis Sci. 2016;57(4):1839–46. doi: 10.1167/iovs.15-18572 27082298.

8. Sarks J, Arnold J, Ho IV, Sarks S, Killingsworth M. Evolution of reticular pseudodrusen. Br J Ophthalmol. 2011;95(7):979–85. doi: 10.1136/bjo.2010.194977 21109695.

9. Lim J, Yue Z. Neuronal aggregates: formation, clearance, and spreading. Dev Cell. 2015;32(4):491–501. doi: 10.1016/j.devcel.2015.02.002 25710535

10. Guo JL, Lee VM. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med. 2014;20(2):130–8. doi: 10.1038/nm.3457 24504409

11. Holmes BB, Diamond MI. Cellular mechanisms of protein aggregate propagation. Curr Opin Neurol. 2012;25(6):721–6. doi: 10.1097/WCO.0b013e32835a3ee0 23108252

12. Bhat SP, Gangalum RK. Secretion of alphaB-Crystallin via exosomes: New clues to the function of human retinal pigment epithelium. Commun Integr Biol. 2011;4(6):739–41. doi: 10.4161/cib.17610 22446542

13. Saman S, Kim W, Raya M, Visnick Y, Miro S, Saman S, et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem. 2012;287(6):3842–9. doi: 10.1074/jbc.M111.277061 22057275

14. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci. 2010;30(20):6838–51. doi: 10.1523/JNEUROSCI.5699-09.2010 20484626

15. Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener. 2012;7:42. doi: 10.1186/1750-1326-7-42 22920859

16. van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28. doi: 10.1038/nrm.2017.125 29339798.

17. Zhang M, Windheim M, Roe SM, Peggie M, Cohen P, Prodromou C, et al. Chaperoned ubiquitylation—crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex. Mol Cell. 2005;20(4):525–38. doi: 10.1016/j.molcel.2005.09.023 16307917.

18. Xu Z, Kohli E, Devlin KI, Bold M, Nix JC, Misra S. Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes. BMC Struct Biol. 2008;8:26. doi: 10.1186/1472-6807-8-26 18485199

19. Murata S, Minami Y, Minami M, Chiba T, Tanaka K. CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2001;2(12):1133–8. doi: 10.1093/embo-reports/kve246 11743028

20. Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003;426(6968):895–9. doi: 10.1038/nature02263 14685250.

21. Shin Y, Klucken J, Patterson C, Hyman BT, McLean PJ. The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways. J Biol Chem. 2005;280(25):23727–34. doi: 10.1074/jbc.M503326200 15845543.

22. Ferreira JV, Fofo H, Bejarano E, Bento CF, Ramalho JS, Girao H, et al. STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy. Autophagy. 2013;9(9):1349–66. doi: 10.4161/auto.25190 23880665.

23. Ferreira JV, Soares AR, Ramalho JS, Pereira P, Girao H. K63 linked ubiquitin chain formation is a signal for HIF1A degradation by Chaperone-Mediated Autophagy. Sci Rep. 2015;5:10210. doi: 10.1038/srep10210 25958982

24. Arndt V, Rogon C, Hohfeld J. To be, or not to be—molecular chaperones in protein degradation. Cell Mol Life Sci. 2007;64(19–20):2525–41. doi: 10.1007/s00018-007-7188-6 17565442.

25. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, et al. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol. 2001;3(1):93–6. doi: 10.1038/35050618 11146632.

26. Cyr DM, Hohfeld J, Patterson C. Protein quality control: U-box-containing E3 ubiquitin ligases join the fold. Trends Biochem Sci. 2002;27(7):368–75. doi: 10.1016/s0968-0004(02)02125-4 12114026.

27. Murata S, Chiba T, Tanaka K. CHIP: a quality-control E3 ligase collaborating with molecular chaperones. Int J Biochem Cell Biol. 2003;35(5):572–8. doi: 10.1016/s1357-2725(02)00394-1 12672450.

28. Petrucelli L, Dickson D, Kehoe K, Taylor J, Snyder H, Grover A, et al. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. Hum Mol Genet. 2004;13(7):703–14. doi: 10.1093/hmg/ddh083 14962978.

29. Dai Q, Zhang C, Wu Y, McDonough H, Whaley RA, Godfrey V, et al. CHIP activates HSF1 and confers protection against apoptosis and cellular stress. EMBO J. 2003;22(20):5446–58. doi: 10.1093/emboj/cdg529 14532117

30. Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C. CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature. 2006;440(7083):551–5. doi: 10.1038/nature04600 16554822

31. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12(1):19–30; sup pp 1–13. Epub 2009/12/08. doi: 10.1038/ncb2000 19966785.

32. Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L. Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc Natl Acad Sci U S A. 2002;99(20):12847–52. doi: 10.1073/pnas.202365899 12239347

33. Holmberg CI, Hietakangas V, Mikhailov A, Rantanen JO, Kallio M, Meinander A, et al. Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J. 2001;20(14):3800–10. doi: 10.1093/emboj/20.14.3800 11447121

34. Reinke H, Saini C, Fleury-Olela F, Dibner C, Benjamin IJ, Schibler U. Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor. Genes Dev. 2008;22(3):331–45. doi: 10.1101/gad.453808 18245447

35. Bento CF, Fernandes R, Ramalho J, Marques C, Shang F, Taylor A, et al. The chaperone-dependent ubiquitin ligase CHIP targets HIF-1alpha for degradation in the presence of methylglyoxal. PLoS One. 2010;5(11):e15062. doi: 10.1371/journal.pone.0015062 21124777

36. Lasser C, Eldh M, Lotvall J. Isolation and characterization of RNA-containing exosomes. J Vis Exp. 2012;(59):e3037. doi: 10.3791/3037 22257828

37. Consortium E-T, Van Deun J, Mestdagh P, Agostinis P, Akay O, Anand S, et al. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research. Nat Methods. 2017;14(3):228–32. Epub 2017/03/01. doi: 10.1038/nmeth.4185 28245209.

38. Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol. 2009;11(9):1143–9. doi: 10.1038/ncb1929 19684575.

39. Takayama K, Matsuura A, Itakura E. Dissection of ubiquitinated protein degradation by basal autophagy. FEBS Lett. 2017;591(9):1199–211. doi: 10.1002/1873-3468.12641 28369861

40. Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. Epub 2019/01/15. doi: 10.1080/20013078.2018.1535750 30637094

41. Chettimada S, Lorenz DR, Misra V, Dillon ST, Reeves RK, Manickam C, et al. Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy. Sci Rep. 2018;8(1):7227. doi: 10.1038/s41598-018-25515-4 29740045

42. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci U S A. 2016;113(8):E968–77. Epub 2016/02/10. doi: 10.1073/pnas.1521230113 26858453

43. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003;300(5618):486–9. doi: 10.1126/science.1079469 12702875.

44. Miao Y, Li G, Zhang X, Xu H, Abraham SN. A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion. Cell. 2015;161(6):1306–19. doi: 10.1016/j.cell.2015.05.009 26027738

45. Kloft N, Neukirch C, von Hoven G, Bobkiewicz W, Weis S, Boller K, et al. A subunit of eukaryotic translation initiation factor 2alpha-phosphatase (CreP/PPP1R15B) regulates membrane traffic. J Biol Chem. 2012;287(42):35299–317. doi: 10.1074/jbc.M112.379883 22915583

46. Vilchez D, Saez I, Dillin A. The role of protein clearance mechanisms in organismal ageing and age-related diseases. Nat Commun. 2014;5:5659. doi: 10.1038/ncomms6659 25482515.

47. Atienzar-Aroca S, Flores-Bellver M, Serrano-Heras G, Martinez-Gil N, Barcia JM, Aparicio S, et al. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J Cell Mol Med. 2016;20(8):1457–66. doi: 10.1111/jcmm.12834 26999719

48. Fernandes R, Hosoya K, Pereira P. Reactive oxygen species downregulate glucose transport system in retinal endothelial cells. Am J Physiol Cell Physiol. 2011;300(4):C927–36. doi: 10.1152/ajpcell.00140.2010 21228321.

49. Fujimoto M, Takaki E, Hayashi T, Kitaura Y, Tanaka Y, Inouye S, et al. Active HSF1 significantly suppresses polyglutamine aggregate formation in cellular and mouse models. J Biol Chem. 2005;280(41):34908–16. doi: 10.1074/jbc.M506288200 16051598.

50. Tawo R, Pokrzywa W, Kevei E, Akyuz ME, Balaji V, Adrian S, et al. The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover. Cell. 2017;169(3):470–82 e13. doi: 10.1016/j.cell.2017.04.003 28431247

51. Min JN, Whaley RA, Sharpless NE, Lockyer P, Portbury AL, Patterson C. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol. 2008;28(12):4018–25. doi: 10.1128/MCB.00296-08 18411298

52. Hoffmann AC, Minakaki G, Menges S, Salvi R, Savitskiy S, Kazman A, et al. Extracellular aggregated alpha synuclein primarily triggers lysosomal dysfunction in neural cells prevented by trehalose. Sci Rep. 2019;9(1):544. Epub 2019/01/27. doi: 10.1038/s41598-018-35811-8 30679445

53. Ferreira DG, Temido-Ferreira M, Vicente Miranda H, Batalha VL, Coelho JE, Szego EM, et al. alpha-synuclein interacts with PrP(C) to induce cognitive impairment through mGluR5 and NMDAR2B. Nat Neurosci. 2017;20(11):1569–79. Epub 2017/09/26. doi: 10.1038/nn.4648 28945221.

Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis

Souhrn

Klíčová slova:

Zdroje

PLOS One

Aktuální možnosti diagnostiky a léčby litiáz