An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function

EMBO Journal

Volumn 36, Issue 12, 2017, Pages 1669-1687

  Mateju, Daniel ^a   Franzmann, Titus M ^a   Patel, Avinash ^a   Kopach, Andrii ^a   Boczek, Edgar E ^a   Maharana, Shovamayee ^a   Lee, Hyun O ^a   Carra, Serena ^b   Hyman, Anthony A ^a   Alberti, Simon ^a  

^a MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

^b UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

protein aggregation; protein misfolding; proteostasis; SOD1; stress granules

Indexed keywords

BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; CHAPERONE; COPPER ZINC SUPEROXIDE DISMUTASE; SOD1 PROTEIN, HUMAN;

AGGRESOME; ARTICLE; AUTOPHAGY; BACTERIAL ARTIFICIAL CHROMOSOME; CELL GRANULE; CONTROLLED STUDY; FEMALE; HEAT STRESS; HUMAN; HUMAN CELL; HYDROPHOBICITY; IMMUNOFLUORESCENCE; PHASE SEPARATION; PHASE TRANSITION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN MISFOLDING; PROTEIN QUALITY; STRESS GRANULE; EPITHELIUM CELL; HELA CELL LINE; METABOLISM; PHYSIOLOGY;

CYTOPLASMIC GRANULES; EPITHELIAL CELLS; HELA CELLS; HUMANS; MOLECULAR CHAPERONES; SUPEROXIDE DISMUTASE-1;

EID: 85017348777     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201695957     Document Type: Article

References (78)

1. Anderson P, Kedersha N (2008) Stress granules: the Tao of RNA triage. Trends Biochem Sci 33: 141–150
2. Aulas A, Vande Velde C (2015) Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS? Front Cell Neurosci 9: 423
3. Bentmann E, Haass C, Dormann D (2013) Stress granules in neurodegeneration – lessons learnt from TAR DNA binding protein of 43 kDa and fused in sarcoma. FEBS J 280: 4348–4370
4. Betting J, Seufert W (1996) A yeast Ubc9 mutant protein with temperature-sensitive in vivo function is subject to conditional proteolysis by a ubiquitin- and proteasome-dependent pathway. J Biol Chem 271: 25790–25796
5. Bolte S, Cordelières FP (2006) A guided tour into subcellular colocalization analysis in light microscopy. J Microsc 224: 213–232
6. Bounedjah O, Desforges B, Wu T-D, Pioche-Durieu C, Marco S, Hamon L, Curmi PA, Guerquin-Kern J-L, Piétrement O, Pastré D (2014) Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules. Nucleic Acids Res 42: 8678–8691
7. Brangwynne CP, Eckmann CR, Courson DS, Rybarska A, Hoege C, Gharakhani J, Jülicher F, Hyman AA (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324: 1729–1732
8. Brangwynne CP, Tompa P, Pappu RV (2015) Polymer physics of intracellular phase transitions. Nat Phys 11: 899–904
9. Buchan JR, Parker R (2009) Eukaryotic stress granules: the ins and outs of translation. Mol Cell 36: 932–941
10. Buchan JR, Kolaitis R-M, Taylor JP, Parker R (2013) Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153: 1461–1474
11. Bunton-Stasyshyn RKA, Saccon RA, Fratta P, Fisher EMC (2015) SOD1 function and its implications for amyotrophic lateral sclerosis pathology: new and renascent themes. Neuroscientist 21: 519–529
12. Chattopadhyay M, Valentine JS (2009) Aggregation of copper-zinc superoxide dismutase in familial and sporadic ALS. Antioxid Redox Signal 11: 1603–1614
13. Cherkasov V, Hofmann S, Druffel-Augustin S, Mogk A, Tyedmers J, Stoecklin G, Bukau B (2013) Coordination of translational control and protein homeostasis during severe heat stress. Curr Biol 23: 2452–2462
14. Corcoran LJ, Mitchison TJ, Liu Q (2004) A novel action of histone deacetylase inhibitors in a protein aggresome disease model. Curr Biol 14: 488–492
15. Costes SV, Daelemans D, Cho EH, Dobbin Z, Pavlakis G, Lockett S (2004) Automatic and quantitative measurement of protein-protein colocalization in live cells. Biophys J 86: 3993–4003
16. Darnell RB (2013) RNA protein interaction in neurons. Annu Rev Neurosci 36: 243–270
17. Decker CJ, Teixeira D, Parker R (2007) Edc3p and a glutamine/asparagine-rich domain of Lsm4p function in processing body assembly in Saccharomyces cerevisiae. J Cell Biol 179: 437–449
18. Deng H-X, Chen W, Hong S-T, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL et al (2011) Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477: 211–215
19. Dewey CM, Cenik B, Sephton CF, Johnson BA, Herz J, Yu G (2012) TDP-43 aggregation in neurodegeneration: are stress granules the key? Brain Res 1462: 16–25
20. Elbaum-Garfinkle S, Kim Y, Szczepaniak K, Chen CC-H, Eckmann CR, Myong S, Brangwynne CP (2015) The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. Proc Natl Acad Sci USA 112: 7189–7194
21. Elden AC, Kim H-J, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rüb U, Auburger G, Trojanowski JQ, Lee VM-Y et al (2010) Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466: 1069–1075
22. Fortun J, Dunn WA Jr, Joy S, Li J, Notterpek L (2003) Emerging role for autophagy in the removal of aggresomes in Schwann cells. J Neurosci 23: 10672–10680
23. Gal J, Kuang L, Barnett KR, Zhu BZ, Shissler SC, Korotkov KV, Hayward LJ, Kasarskis EJ, Zhu H (2016) ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics. Acta Neuropathol 132: 563–576.
24. Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C (2011) BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep 12: 149–156
25. Ganassi M, Mateju D, Bigi I, Mediani L, Poser I, Lee HO, Seguin SJ, Morelli FF, Vinet J, Leo G, Pansarasa O, Cereda C, Poletti A, Alberti S, Carra S (2016) A surveillance function of the HSPB8-BAG3-HSP70 chaperone complex ensures stress granule integrity and dynamism. Mol Cell 63: 796–810
26. García-Mata R, Bebök Z, Sorscher EJ, Sztul ES (1999) Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. J Cell Biol 146: 1239–1254
27. Gilks N, Kedersha N, Ayodele M, Shen L, Stoecklin G, Dember LM, Anderson P (2004) Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol Biol Cell 15: 5383–5398
28. Goggin K, Beaudoin S, Grenier C, Brown A-A, Roucou X (2008) Prion protein aggresomes are poly(A)+ ribonucleoprotein complexes that induce a PKR-mediated deficient cell stress response. Biochim Biophys Acta 1783: 479–491
29. Han TW, Kato M, Xie S, Wu LC, Mirzaei H, Pei J, Chen M, Xie Y, Allen J, Xiao G, McKnight SL (2012) Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell 149: 768–779
30. Hyman AA, Weber CA, Jülicher F (2014) Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol 30: 39–58
31. Iwata A, Riley BE, Johnston JA, Kopito RR (2005) HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem 280: 40282–40292
32. Jain S, Wheeler JR, Walters RW, Agrawal A, Barsic A, Parker R (2016) ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164: 487–498.
33. Johnston JA, Ward CL, Kopito RR (1998) Aggresomes: a cellular response to misfolded proteins. J Cell Biol 143: 1883–1898
34. Johnston JA, Dalton MJ, Gurney ME, Kopito RR (2000) Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 97: 12571–12576
35. Kaganovich D, Kopito R, Frydman J (2008) Misfolded proteins partition between two distinct quality control compartments. Nature 454: 1088–1095
36. Kato M, Han TW, Xie S, Shi K, Du X, Wu LC, Mirzaei H, Goldsmith EJ, Longgood J, Pei J, Grishin NV, Frantz DE, Schneider JW, Chen S, Li L, Sawaya MR, Eisenberg D, Tycko R, McKnight SL (2012) Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149: 753–767
37. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP (2003) The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115: 727–738
38. Kedersha NL, Gupta M, Li W, Miller I, Anderson P (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol 147: 1431–1442
39. Kedersha N, Cho MR, Li W, Yacono PW, Chen S, Gilks N, Golan DE, Anderson P (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol 151: 1257–1268
40. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, Scheuner D, Kaufman RJ, Golan DE, Anderson P (2005) Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 169: 871–884
41. Kim HJ, Kim NC, Wang Y-D, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN et al (2013a) Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495: 467–473
42. Kim YE, Hipp MS, Bracher A, Hayer-Hartl M, Ulrich Hartl F (2013b) Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem 82: 323–355
43. Kroschwald S, Maharana S, Mateju D, Malinovska L, Nüske E, Poser I, Richter D, Alberti S (2015) Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules. Elife 4: e06807
44. Kwon S, Zhang Y, Matthias P (2007) The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev 21: 3381–3394
45. Li P, Banjade S, Cheng H-C, Kim S, Chen B, Guo L, Llaguno M, Hollingsworth JV, King DS, Banani SF, Russo PS, Jiang Q-X, Nixon BT, Rosen MK (2012) Phase transitions in the assembly of multivalent signalling proteins. Nature 483: 336–340
46. Li YR, King OD, Shorter J, Gitler AD (2013) Stress granules as crucibles of ALS pathogenesis. J Cell Biol 201: 361–372
47. Lin Y, Protter DSW, Rosen MK, Parker R (2015) Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol Cell 60: 208–219
48. Liu J, Xu Y, Stoleru D, Salic A (2012) Imaging protein synthesis in cells and tissues with an alkyne analog of puromycin. Proc Natl Acad Sci USA 109: 413–418
49. Lu L, Wang S, Zheng L, Li X, Suswam EA, Zhang X, Wheeler CG, Nabors LB, Filippova N, King PH (2009) Amyotrophic lateral sclerosis-linked mutant SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR): implications for impaired post-transcriptional regulation of vascular endothelial growth factor. J Biol Chem 284: 33989–33998
50. Majcher V, Goode A, James V, Layfield R (2015) Autophagy receptor defects and ALS-FTLD. Mol Cell Neurosci 66: 43–52
51. Mitchell SF, Parker R (2014) Principles and properties of eukaryotic mRNPs. Mol Cell 54: 547–558
52. Mollet S, Cougot N, Wilczynska A, Dautry F, Kress M, Bertrand E, Weil D (2008) Translationally repressed mRNA transiently cycles through stress granules during stress. Mol Biol Cell 19: 4469–4479
53. Molliex A, Temirov J, Lee J, Coughlin M, Kanagaraj AP, Kim HJ, Mittag T, Taylor JP (2015) Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163: 123–133
54. Murakami T, Qamar S, Lin JQ, Schierle GSK, Rees E, Miyashita A, Costa AR, Dodd RB, Chan FTS, Michel CH, Kronenberg-Versteeg D, Li Y, Yang S-P, Wakutani Y, Meadows W, Ferry RR, Dong L, Tartaglia GG, Favrin G, Lin W-L et al (2015) ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function. Neuron 88: 678–690
55. Patel A, Lee HO, Jawerth L, Maharana S, Jahnel M, Hein MY, Stoynov S, Mahamid J, Saha S, Franzmann TM, Pozniakovski A, Poser I, Maghelli N, Royer LA, Weigert M, Myers EW, Grill S, Drechsel D, Hyman AA, Alberti S (2015) A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162: 1066–1077
56. Poser I, Sarov M, Hutchins JRA, Hériché J-K, Toyoda Y, Pozniakovsky A, Weigl D, Nitzsche A, Hegemann B, Bird AW, Pelletier L, Kittler R, Hua S, Naumann R, Augsburg M, Sykora MM, Hofemeister H, Zhang Y, Nasmyth K, White KP et al (2008) BAC transgeneOmics: a high-throughput method for exploration of protein function in mammals. Nat Methods 5: 409–415
57. Prudencio M, Hart PJ, Borchelt DR, Andersen PM (2009) Variation in aggregation propensities among ALS-associated variants of SOD1: correlation to human disease. Hum Mol Genet 18: 3217–3226
58. Rakhit R, Robertson J, Velde CV, Horne P, Ruth DM, Griffin J, Cleveland DW, Cashman NR, Chakrabartty A (2007) An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS. Nat Med 13: 754–759
59. Ramaswami M, Taylor JP, Parker R (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154: 727–736
60. Rapsomaniki MA, Kotsantis P, Symeonidou I-E, Giakoumakis N-N, Taraviras S, Lygerou Z (2012) EasyFRAP: an interactive, easy-to-use tool for qualitative and quantitative analysis of FRAP data. Bioinformatics 28: 1800–1801
61. Robberecht W, Philips T (2013) The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 14: 248–264
62. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez J-Y, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9: 676–682
63. Schmid B, Schindelin J, Cardona A, Longair M, Heisenberg M (2010) A high-level 3D visualization API for Java and ImageJ. BMC Bioinformatics 11: 274
64. Seguin SJ, Morelli FF, Vinet J, Amore D, De Biasi S, Poletti A, Rubinsztein DC, Carra S (2014) Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly. Cell Death Differ 21: 1838–1851
65. Singh G, Pratt G, Yeo GW, Moore MJ (2015) The clothes make the mRNA: past and present trends in mRNP fashion. Annu Rev Biochem 84: 325–354
66. Stevens JC, Chia R, Hendriks WT, Bros-Facer V, van Minnen J, Martin JE, Jackson GS, Greensmith L, Schiavo G, Fisher EMC (2010) Modification of superoxide dismutase 1 (SOD1) properties by a GFP tag–implications for research into amyotrophic lateral sclerosis (ALS). PLoS ONE 5: e9541
67. Sumi H, Kato S, Mochimaru Y, Fujimura H, Etoh M, Sakoda S (2009) Nuclear TAR DNA binding protein 43 expression in spinal cord neurons correlates with the clinical course in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 68: 37–47
68. Taylor JP, Tanaka F, Robitschek J, Sandoval CM, Taye A, Markovic-Plese S, Fischbeck KH (2003) Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum Mol Genet 12: 749–757
69. Taylor RC, Dillin A (2011) Aging as an event of proteostasis collapse. Cold Spring Harb Perspect Biol 3: a004440
70. Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo J-M et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323: 1208–1211
71. Vanderweyde T, Yu H, Varnum M, Liu-Yesucevitz L, Citro A, Ikezu T, Duff K, Wolozin B (2012) Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies. J Neurosci 32: 8270–8283
72. Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, Lehrach H, Wanker EE (2001) Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 12: 1393–1407
73. Wallace EWJ, Kear-Scott JL, Pilipenko EV, Schwartz MH, Laskowski PR, Rojek AE, Katanski CD, Riback JA, Dion MF, Franks AM, Airoldi EM, Pan T, Budnik BA, Drummond DA (2015) Reversible, specific, active aggregates of endogenous proteins assemble upon heat stress. Cell 162: 1286–1298
74. Walters RW, Muhlrad D, Garcia J, Parker R (2015) Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae. RNA 21: 1660–1671
75. Weisberg SJ, Lyakhovetsky R, Werdiger A-C, Gitler AD, Soen Y, Kaganovich D (2012) Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity. Proc Natl Acad Sci USA 109: 15811–15816
76. Wolozin B (2012) Regulated protein aggregation: stress granules and neurodegeneration. Mol Neurodegener 7: 56
77. Yung C, Sha D, Li L, Chin L-S (2015) Parkin protects against misfolded SOD1 toxicity by promoting its aggresome formation and autophagic clearance. Mol Neurobiol 53: 6270–6287
78. Zhang H, Elbaum-Garfinkle S, Langdon EM, Taylor N, Occhipinti P, Bridges AA, Brangwynne CP, Gladfelter AS (2015) RNA controls polyQ protein phase transitions. Mol Cell 60: 220–230