Dynamic droplets: The role of cytoplasmic inclusions in stress, function, and disease

Cellular and Molecular Life Sciences

Volumn 72, Issue 3, 2015, Pages 401-415

  Amen, Triana ^a   Kaganovich, Daniel ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Aggregation; Aggresome; Chaperone; Dynamic droplets; Inclusion; Inclusion body; IPOD; JUNQ; Misfolded protein; P bodies; PhoC; Proteasome; Stress foci; Stress granules; Ubiquitin

Indexed keywords

AMYLOID PROTEIN; ATAXIN 1; DYNAMIC DROPLET; FAS ANTIGEN; FUSED IN SARCOMA PROTEIN; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 104; HEAT SHOCK PROTEIN 110; HEAT SHOCK PROTEIN 26; HEAT SHOCK PROTEIN 42; HEAT SHOCK PROTEIN 70; HISTONE DEACETYLASE 6; INITIATION FACTOR 4E; PHOSPHOPROTEIN; PROTEIN; PROTEIN P62; RIBONUCLEOPROTEIN; TAR DNA BINDING PROTEIN; TRISTETRAPROLIN; UNCLASSIFIED DRUG; PROTEIN AGGREGATE;

AGGRESOME; AGING; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CELL COMPARTMENTALIZATION; CELL FUNCTION; CELL GRANULE; CELL INCLUSION; CELL PH; CELL STRESS; CELL STRUCTURE; DEGENERATIVE DISEASE; DISEASE MODEL; HOMEOSTASIS; HUMAN; INTRACELLULAR SPACE; IPOD COMPARTMENT; JUNQ COMPARTMENT; MOLECULAR PATHOLOGY; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; PHASE TRANSITION; PROTEIN AGGREGATION; PROTEIN ASSEMBLY; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MISFOLDING; PROTEIN PROCESSING; PROTEIN STRUCTURE; REJUVENATION; RNA METABOLISM; RNA TRANSLATION; STRESS FOCI; STRUCTURE ACTIVITY RELATION; UBIQUITINATION; ANIMAL; BIOLOGICAL MODEL; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGICAL STRESS; PHYSIOLOGY; PROTEOSTASIS DEFICIENCY;

AGING; ANIMALS; HOMEOSTASIS; HUMANS; INCLUSION BODIES; MODELS, BIOLOGICAL; PROTEIN AGGREGATES; PROTEOSTASIS DEFICIENCIES; STRESS, PHYSIOLOGICAL;

EID: 84921936587     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-014-1740-y     Document Type: Article

References (136)

1. Aguzzi A, O'Connor T (2010) Protein aggregation diseases: pathogenicity and therapeutic perspectives. Nat Rev Drug Discov 9(3):237-248. doi: 10.1038/nrd3050nrd3050
2. Renner M, Melki R (2014) Protein aggregation and prionopathies. Pathol Biol (Paris) 62(3):162-168. doi: 10.1016/j.patbio.2014.01.003
3. Rajan RS, Illing ME, Bence NF, Kopito RR (2001) Specificity in intracellular protein aggregation and inclusion body formation. Proc Natl Acad Sci USA 98(23):13060-13065. doi: 10.1073/pnas.181479798181479798
4. Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10(12):524-530
5. Johnston JA, Ward CL, Kopito RR (1998) Aggresomes: a cellular response to misfolded proteins. J Cell Biol 143(7):1883-1898
6. Cotto J, Fox S, Morimoto R (1997) HSF1 granules: a novel stress-induced nuclear compartment of human cells. J Cell Sci 110(Pt 23):2925-2934
7. Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI (2002) Polyglutamine protein aggregates are dynamic. Nat Cell Biol 4(10):826-831. doi: 10.1038/ncb863ncb863
8. Matsumoto G, Kim S, Morimoto RI (2006) Huntingtin and mutant SOD1 form aggregate structures with distinct molecular properties in human cells. J Biol Chem 281(7):4477-4485. doi: 10.1074/jbc.M509201200
9. Perez MK, Paulson HL, Pendse SJ, Saionz SJ, Bonini NM, Pittman RN (1998) Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol 143(6):1457-1470. doi: 10.1083/jcb.143.6.1457
10. Alves-Rodrigues A, Gregori L, Figueiredo-Pereira ME (1998) Ubiquitin, cellular inclusions and their role in neurodegeneration. Trends Neurosci 21(12):516-520. doi: 10.1016/S0166-2236(98)01276-4
11. Treusch S, Cyr DM, Lindquist S (2009) Amyloid deposits: protection against toxic protein species? Cell Cycle 8(11):1668-1674
12. Krobitsch S, Lindquist S (2000) Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc Natl Acad Sci USA 97(4):1589-1594
13. Nathan DF, Vos MH, Lindquist S (1997) In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc Natl Acad Sci USA 94(24):12949-12956
14. Bruijn LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Ohama E, Reaume AG, Scott RW, Cleveland DW (1998) Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 281(5384):1851-1854. doi: 10.1126/science.281.5384.1851
15. Cleveland DW, Liu J (2000) Oxidation versus aggregation - how do SOD1 mutants cause ALS? Nat Med 6(12):1320-1321. doi: 10.1038/82122
16. Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ (2008) Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS ONE 3(4):e1867. doi: 10.1371/journal.pone.0001867
17. Ben-Gedalya T, Cohen E (2012) Quality control compartments coming of age. Traffic 13(5):635-642. doi: 10.1111/j.1600-0854.2012.01330.x
18. Dillin A, Cohen E (2011) Ageing and protein aggregation-mediated disorders: from invertebrates to mammals. Philos Trans R Soc Lond B Biol Sci 366(1561):94-98. doi: 10.1098/rstb.2010.0271366/1561/94
19. England JL, Kaganovich D (2011) Polyglutamine shows a urea-like affinity for unfolded cytosolic protein. FEBS Lett 585(2):381-384. doi: 10.1016/j.febslet.2010.12.023
20. Lin WL, Dickson DW (2012) Ultrastructure of ubiquitin-positive, TDP-43-negative neuronal inclusions in cerebral cortex of C9ORF72-linked frontotemporal lobar degeneration/amyotrophic lateral sclerosis. Neuropathology 32(6):679-681. doi: 10.1111/j.1440-1789.2012.01305.x
21. Waxman EA, Giasson BI (2011) Induction of intracellular tau aggregation is promoted by alpha-synuclein seeds and provides novel insights into the hyperphosphorylation of tau. J Neurosci 31(21):7604-7618. doi: 10.1523/Jneurosci.0297-11.2011
22. Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, Chatterjee A, Hurtig HI, Karlawish JH, Rosen HJ, Van Deerlin V, Lee VM, Miller BL, Trojanowski JQ, Grossman M (2006) Frontotemporal dementia: clinicopathological correlations. Ann Neurol 59(6):952-962. doi: 10.1002/ana.20873
23. Frid P, Anisimov SV, Popovic N (2007) Congo red and protein aggregation in neurodegenerative diseases. Brain Res Rev 53(1):135-160. doi: 10.1016/j.brainresrev.2006.08.001
24. Bhat KP, Yan S, Wang CE, Li S, Li XJ (2014) Differential ubiquitination and degradation of huntingtin fragments modulated by ubiquitin-protein ligase E3A. Proc Natl Acad Sci USA 111(15):5706-5711. doi: 10.1073/pnas.14022151111402215111
25. Sampaio-Marques B, Felgueiras C, Silva A, Rodrigues M, Tenreiro S, Franssens V, Reichert AS, Outeiro TF, Winderickx J, Ludovico P (2012) SNCA (alpha-synuclein)-induced toxicity in yeast cells is dependent on sirtuin 2 (Sir2)-mediated mitophagy. Autophagy 8(10):1494-1509. doi: 10.4161/Auto.21275
26. Zondler L, Miller-Fleming L, Repici M, Goncalves S, Tenreiro S, Rosado-Ramos R, Betzer C, Straatman KR, Jensen PH, Giorgini F, Outeiro TF (2014) DJ-1 interactions with alpha-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. Cell Death Dis 5:e1350. doi: 10.1038/cddis.2014.307cddis2014307
27. Gidalevitz T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI (2006) Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311(5766):1471-1474. doi: 10.1126/science.1124514
28. Morley JF, Brignull HR, Weyers JJ, Morimoto RI (2002) The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci USA 99(16):10417-10422. doi: 10.1073/pnas.152161099152161099
29. Volovik Y, Marques FC, Cohen E (2014) The nematode Caenorhabditis elegans: a versatile model for the study of proteotoxicity and aging. Methods 68(3):458-464. doi: 10.1016/j.ymeth.2014.04.014
30. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A (2006) Opposing activities protect against age-onset proteotoxicity. Science 313(5793):1604-1610. doi: 10.1126/science.1124646
31. Douglas PM, Treusch S, Ren HY, Halfmann R, Duennwald ML, Lindquist S, Cyr DM (2008) Chaperone-dependent amyloid assembly protects cells from prion toxicity. Proc Natl Acad Sci USA 105(20):7206-7211. doi: 10.1073/pnas.08025931050802593105
32. Johnson BS, McCaffery JM, Lindquist S, Gitler AD (2008) A yeast TDP-43 proteinopathy model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc Natl Acad Sci USA 105(17):6439-6444. doi: 10.1073/pnas.08020821050802082105
33. Liu J, Shinobu LA, Ward CM, Young D, Cleveland DW (2005) Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis. J Neurochem 93(4):875-882. doi: 10.1111/j.1471-4159.2005.03054.x
34. Parone PA, Da Cruz S, Han JS, McAlonis-Downes M, Vetto AP, Lee SK, Tseng E, Cleveland DW (2013) Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis. J Neurosci 33(11):4657-4671. doi: 10.1523/Jneurosci.1119-12.2013
35. D'Angelo F, Vignaud H, Di Martino J, Salin B, Devin A, Cullin C, Marchal C (2013) A yeast model for amyloid-beta aggregation exemplifies the role of membrane trafficking and PICALM in cytotoxicity. Dis Model Mech 6(1):206-216. doi: 10.1242/dmm.010108dmm.010108
36. Miller J, Arrasate M, Shaby BA, Mitra S, Masliah E, Finkbeiner S (2010) Quantitative relationships BETWEEN huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into Huntington's disease molecular pathogenesis. J Neurosci 30(31):10541-10550. doi: 10.1523/Jneurosci.0146-10.2010
37. Nucifora LG, Burke KA, Feng X, Arbez N, Zhu S, Miller J, Yang G, Ratovitski T, Delannoy M, Muchowski PJ, Finkbeiner S, Legleiter J, Ross CA, Poirier MA (2012) Identification of novel potentially toxic oligomers formed in vitro from mammalian-derived expanded huntingtin exon-1 protein. J Biol Chem 287(19):16017-16028. doi: 10.1074/jbc.M111.252577M111.252577
38. Kryndushkin D, Ihrke G, Piermartiri TC, Shewmaker F (2012) A yeast model of optineurin proteinopathy reveals a unique aggregation pattern associated with cellular toxicity. Mol Microbiol 86(6):1531-1547. doi: 10.1111/mmi.12075
39. Brangwynne CP, Koenderink GH, MacKintosh FC, Weitz DA (2008) Cytoplasmic diffusion: molecular motors mix it up. J Cell Biol 183(4):583-587. doi: 10.1083/jcb.200806149
40. Hyman AA, Brangwynne CP (2011) Beyond stereospecificity: liquids and mesoscale organization of cytoplasm. Dev Cell 21(1):14-16. doi: 10.1016/j.devcel.2011.06.013
41. Guo M, Ehrlicher AJ, Jensen MH, Renz M, Moore JR, Goldman RD, Lippincott-Schwartz J, Mackintosh FC, Weitz DA (2014) Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy. Cell 158(4):822-832. doi: 10.1016/j.cell.2014.06.051
42. Weber SC, Spakowitz AJ, Theriot JA (2012) Nonthermal ATP-dependent fluctuations contribute to the in vivo motion of chromosomal loci. P Natl Acad Sci USA 109(19):7338-7343. doi: 10.1073/pnas.1119505109
43. Parry BR, Surovtsev IV, Cabeen MT, O'Hem CS, Dufresne ER, Jacobs-Wagner C (2014) The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity. Cell 156(1-2):183-194. doi: 10.1016/j.cell.2013.11.028
44. Lee CF, Brangwynne CP, Gharakhani J, Hyman AA, Julicher F (2013) Spatial organization of the cell cytoplasm by position-dependent phase separation. Phys Rev Lett 111(26):088101. doi: 10.1103/Physrevlett.111.269902
45. Weber SC, Brangwynne CP (2012) Getting RNA and protein in phase. Cell 149(6):1188-1191. doi: 10.1016/j.cell.2012.05.022
46. Kaganovich D, Kopito R, Frydman J (2008) Misfolded proteins partition between two distinct quality control compartments. Nature 454(7208):U1036-U1088. doi: 10.1038/Nature07195
47. Walter GM, Smith MC, Wisen S, Basrur V, Elenitoba-Johnson KSJ, Duennwald ML, Kumar A, Gestwicki JE (2011) Ordered assembly of heat shock proteins, Hsp26, Hsp70 Hsp90, and Hsp104, on expanded polyglutamine fragments revealed by chemical probes. J Biol Chem 286(47):40486-40493. doi: 10.1074/jbc.M111.284448
48. Haslbeck M, Miess A, Stromer T, Walter S, Buchner J (2005) Disassembling protein aggregates in the yeast cytosol: the cooperation of Hsp26 with SSA1 and Hsp104. J Biol Chem 280(25):23861-23868. doi: 10.1074/jbc.M502697200
49. Alberti S (2012) Molecular mechanisms of spatial protein quality control. Prion 6(5):2-4. doi: 10.4161/Pri.22470
50. Shiber A, Breuer W, Brandeis M, Ravid T (2013) Ubiquitin conjugation triggers misfolded protein sequestration into quality control foci when Hsp70 chaperone levels are limiting. Mol Biol Cell 24(13):2076-2087. doi: 10.1091/mbc.E13-01-0010
51. Spokoini R, Moldavski O, Nahmias Y, England JL, Schuldiner M, Kaganovich D (2012) Confinement to organelle-associated inclusion structures mediates asymmetric inheritance of aggregated protein in budding yeast. Cell Rep 2(4):738-747. doi: 10.1016/j.celrep.2012.08.024
52. Ogrodnik M, Salmonowicz H, Brown R, Turkowska J, Sredniawa W, Pattabiraman S, Amen T, Abraham AC, Eichler N, Lyakhovetsky R, Kaganovich D (2014) Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin. Proc Natl Acad Sci USA 111(22):8049-8054. doi: 10.1073/pnas.13240351111324035111
53. Weisberg SJ, Lyakhovetsky R, Werdiger AC, Gitler AD, Soen Y, Kaganovich D (2012) Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity. Proc Natl Acad Sci USA 109(39):15811-15816. doi: 10.1073/pnas.1205829109
54. Malinovska L, Kroschwald S, Munder MC, Richter D, Alberti S (2012) Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregates. Mol Biol Cell 23(16):3041-3056. doi: 10.1091/mbc.E12-03-0194
55. Gallagher PS, Oeser ML, Abraham AC, Kaganovich D, Gardner RG (2014) Cellular maintenance of nuclear protein homeostasis. Cell Mol Life Sci 71(10):1865-1879. doi: 10.1007/s00018-013-1530-y
56. Fredrickson EK, Gallagher PS, Candadai SVC, Gardner RG (2013) Substrate recognition in nuclear protein quality control degradation is governed by exposed hydrophobicity that correlates with aggregation and insolubility. J Biol Chem 288(9):6130-6139. doi: 10.1074/jbc.M112.406710
57. Tyedmers J (2012) Patterns of [PSI+] aggregation allow insights into cellular organization of yeast prion aggregates. Prion 6(3):191-200. doi: 10.4161/Pri.18986
58. Treusch S, Lindquist S (2012) An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component. J Cell Biol 197(3):369-379. doi: 10.1083/jcb.201108146
59. Tyedmers J, Treusch S, Dong J, McCaffery JM, Bevis B, Lindquist S (2010) Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation. P Natl Acad Sci USA 107(19):8633-8638. doi: 10.1073/pnas.1003895107
60. Kanneganti V, Kama R, Gerst JE (2011) Btn3 is a negative regulator of Btn2-mediated endosomal protein trafficking and prion curing in yeast. Mol Biol Cell 22(10):1648-1663. doi: 10.1091/mbc.E10-11-0878
61. Polling S, Mok YF, Ramdzan YM, Turner BJ, Yerbury JJ, Hill AF, Hatters DM (2014) Misfolded polyglutamine, polyalanine, and superoxide dismutase 1 aggregate via distinct pathways in the cell. J Biol Chem 289(10):6669-6680. doi: 10.1074/jbc.M113.520189
62. Oling D, Eisele F, Kvint K, Nystrom T (2014) Opposing roles of Ubp3-dependent deubiquitination regulate replicative life span and heat resistance. EMBO J 33(7):747-761. doi: 10.1002/embj.201386822
63. Garcia-Mata R, Bebok Z, Sorscher EJ, Sztul ES (1999) Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. Mol Biol Cell 10:86a
64. Hill SM, Hao X, Liu B, Nystrom T (2014) Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae. Science 344(6190):1389-1392. doi: 10.1126/science.1252634
65. Song J, Yang Q, Yang J, Larsson L, Hao X, Zhu X, Malmgren-Hill S, Cvijovic M, Fernandez-Rodriguez J, Grantham J, Gustafsson CM, Liu B, Nystrom T (2014) Essential genetic interactors of SIR2 required for spatial sequestration and asymmetrical inheritance of protein aggregates. PLoS Genet 10(7):e1004539. doi: 10.1371/journal.pgen.1004539PGENETICS-D-13-03187
66. Petrovska I, Nuske E, Munder MC, Kulasegaran G, Malinovska L, Kroschwald S, Richter D, Fahmy K, Gibson K, Verbavatz JM, Alberti S (2014) Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation. Elife 3:5-11. doi: 10.7554/Elife.02409
67. Ben-Gedalya T, Lyakhovetsky R, Yedidia Y, Bejerano-Sagie M, Kogan NM, Karpuj MV, Kaganovich D, Cohen E (2011) Cyclosporin-A-induced prion protein aggresomes are dynamic quality-control cellular compartments. J Cell Sci 124(Pt 11):1891-1902. doi: 10.1242/jcs.077693jcs.077693
68. Thirumalai D, Reddy G, Straub JE (2012) Role of water in protein aggregation and amyloid polymorphism. Accounts Chem Res 45(1):83-92. doi: 10.1021/Ar2000869
69. 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 170(5):847
70. Stoecklin G, Kedersha N (2013) Relationship of GW/P-bodies with stress granules. Adv Exp Med Biol 768:197-211. doi: 10.1007/978-1-4614-5107-5-12
71. Liu BD, Larsson L, Franssens V, Hao XX, Hill SM, Andersson V, Hoglund D, Song J, Yang XX, Oling D, Grantham J, Winderickx J, Nystrom T (2011) Segregation of protein aggregates involves actin and the polarity machinery. Cell 147(5):959-961. doi: 10.1016/j.cell.2011.11.018
72. Summers DW, Wolfe KJ, Ren HY, Cyr DM (2013) The type II Hsp40 Sis1 cooperates with Hsp70 and the E3 ligase Ubr1 to promote degradation of terminally misfolded cytosolic protein. PLoS ONE 8(1):e52099. doi: 10.1371/journal.pone.0052099PONE-D-12-30428
73. Shorter J, Lindquist S (2004) Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304(5678):1793-1797. doi: 10.1126/science.1098007
74. Shorter J, Lindquist S (2008) Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. EMBO J 27(20):2712-2724. doi: 10.1038/emboj.2008.194
75. DeSantis ME, Leung EH, Sweeny EA, Jackrel ME, Cushman-Nick M, Neuhaus-Follini A, Vashist S, Sochor MA, Knight MN, Shorter J (2012) Operational plasticity enables Hsp104 to disaggregate diverse amyloid and nonamyloid clients. Cell 151(4):778-793. doi: 10.1016/j.cell.2012.09.038
76. Satpute-Krishnan P, Langseth SX, Serio TR (2007) Hsp104-dependent remodeling of prion complexes mediates protein-only inheritance. PLoS Biol 5(2):251-262. doi: 10.1371/journal.pbio.0050024
77. Zaarur N, Meriin AB, Gabai VL, Sherman MY (2008) Triggering aggresome formation. Dissecting aggresome-targeting and aggregation signals in synphilin 1. J Biol Chem 283(41):27575-27584. doi: 10.1074/jbc
78. Zaarur N, Meriin AB, Bejarano E, Xu XB, Gabai VL, Cuervo AM, Sherman MY (2014) Proteasome failure promotes positioning of lysosomes around the aggresome via local block of microtubule-dependent transport. Mol Cell Biol 34(7):1336-1348. doi: 10.1128/Mcb.00103-14
79. Muchowski PJ, Ning K, D'Souza-Schorey C, Fields S (2002) Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment. P Natl Acad Sci USA 99(2):727-732. doi: 10.1073/pnas.022628699
80. Strom AL, Shi P, Zhang FJ, Gal J, Kilty R, Hayward LJ, Zhu HN (2008) Interaction of amyotrophic lateral sclerosis (ALS)-related mutant copper-zinc superoxide dismutase with the dynein-dynactin complex contributes to inclusion formation. J Biol Chem 283(33):22795-22805. doi: 10.1074/jbc.M800276200
81. Yao TP (2010) The role of ubiquitin in autophagy-dependent protein aggregate processing. Genes Cancer 1(7):779-786. doi: 10.1177/1947601910383277
82. Ehrlicher AJ, Nakamura F, Hartwig JH, Weitz DA, Stossel TP (2011) Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin A. Nature 478(7368):260-263 10.1038/nature10430
83. Wustner D, Solanko LM, Lund FW, Sage D, Schroll HJ, Lomholt MA (2012) Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation. BMC Bioinformatics 13:296. doi: 10.1186/1471-2105-13-296
84. Fossati M, Borgese N, Colombo SF, Francolini M (2014) Visualization of endoplasmic reticulum subdomains in cultured cells. J Vis Exp 84:e50985. doi: 10.3791/50985
85. Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD (2012) Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet 21(13):2899-2911. doi: 10.1093/hmg/dds116dds116
86. Gitler AD, Shorter J (2011) RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion 5(3):179-187. doi: 10.4161/pri.5.3.17230
87. West JP 3rd, Gitler AD (2014) Cell biology. Clogging information flow in ALS. Science 345(6201):1118-1119. doi: 10.1126/science.1259461345/6201/1118
88. Hart MP, Brettschneider J, Lee VMY, Trojanowski JQ, Gitler AD (2012) Distinct TDP-43 pathology in ALS patients with ataxin 2 intermediate-length polyQ expansions. Acta Neuropathol 124(2):221-230. doi: 10.1007/s00401-012-0985-5
89. Bonini NM, Gitler AD (2011) Model organisms reveal insight into human neurodegenerative disease: ataxin-2 intermediate-length polyglutamine expansions are a risk factor for ALS. J Mol Neurosci 45(3):676-683. doi: 10.1007/s12031-011-9548-9
90. Li YR, King OD, Shorter J, Gitler AD (2013) Stress granules as crucibles of ALS pathogenesis. J Cell Biol 201(3):361-372. doi: 10.1083/jcb.201302044
91. Gitler AD (2012) TDP-43 and FUS/TLS yield a target-rich haul in ALS. Nat Neurosci 15(11):1467-1469
92. Liu-Yesucevitz L, Lin AY, Ebata A, Boon JY, Reid W, Xu YF, Kobrin K, Murphy GJ, Petrucelli L, Wolozin B (2014) ALS-linked mutations enlarge TDP-43-enriched neuronal RNA granules in the dendritic arbor. J Neurosci 34(12):4167-4174. doi: 10.1523/Jneurosci.2350-13.2014
93. Kim HJ, Raphael AR, LaDow ES, McGurk L, Weber RA, Trojanowski JQ, Lee VM, Finkbeiner S, Gitler AD, Bonini NM (2014) Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet 46(2):152-160. doi: 10.1038/ng.2853ng.2853
94. Wang J, Farr GW, Zeiss CJ, Rodriguez-Gil DJ, Wilson JH, Furtak K, Rutkowski DT, Kaufman RJ, Ruse CI, Yates JR, Perrin S, Feany MB, Horwich AL (2009) Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS. P Natl Acad Sci USA 106(5):1392-1397. doi: 10.1073/pnas.0813045106
95. Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, Horwich AL (2009) An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. Plos Genet 5(1):2-6. doi: 10.1371/journal.pgen.1000350
96. Johnson BS, Snead D, Lee JJ, McCaffery JM, Shorter J (2009) Gitler AD (2009) TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 284(37):25459. doi: 10.1074/jbc.A109.010264
97. Mishra RS, Bose S, Gu Y, Li R, Singh N (2003) Aggresome formation by mutant prion proteins: the unfolding role of proteasomes in familial prion disorders. J Alzheimers Dis 5(1):15-23
98. Swinnen E, Buttner S, Outeiro TF, Galas MC, Madeo F, Winderickx J, Franssens V (2011) Aggresome formation and segregation of inclusions influence toxicity of alpha-synuclein and synphilin-1 in yeast. Biochem Soc Trans 39(5):1476-1481. doi: 10.1042/BST0391476BST0391476
99. Wang H, Ying Z, Wang G (2012) Ataxin-3 regulates aggresome formation of copper-zinc superoxide dismutase (SOD1) by editing K63-linked polyubiquitin chains. J Biol Chem 287(34):28576-28585. doi: 10.1074/jbc.M111.299990M111.299990
100. Adachi H, Kurooka T, Otsu W, Inaba M (2010) The forced aggresome formation of a bovine anion exchanger 1 (AE1) mutant through association with deltaF508-cystic fibrosis transmembrane conductance regulator upon proteasome inhibition in HEK293 cells. Jpn J Vet Res 58(2):101-110
101. Cohen E, Taraboulos A (2003) Scrapie-like prion protein accumulates in aggresomes of cyclosporin A-treated cells. EMBO J 22(3):404-417. doi: 10.1093/Emboj/Cdg045
102. Bounedjah O, Desforges B, Wu TD, Pioche-Durieu C, Marco S, Hamon L, Curmi PA, Guerquin-Kern JL, Pietrement O, Pastre D (2014) Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules. Nucleic Acids Res 42(13):8678-8691. doi: 10.1093/nar/gku582
103. Alberti S, Halfmann R, King O, Kapila A, Lindquist S (2009) A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 137(1):146-158. doi: 10.1016/j.cell.2009.02.044
104. Halfmann R, Alberti S, Lindquist S (2010) Prions, protein homeostasis, and phenotypic diversity. Trends Cell Biol 20(3):125-133. doi: 10.1016/j.tcb.2009.12.003
105. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A (2006) Opposing activities protect against age-onset proteotoxicity. Science 313(5793):1604-1610. doi: 10.1126/science.1124646
106. Prudencio M, Borchelt DR (2011) Superoxide dismutase 1 encoding mutations linked to ALS adopts a spectrum of misfolded states. Mol Neurodegener 6:77. doi: 10.1186/1750-1326-6-771750-1326-6-77
107. Sacino AN, Thomas MA, Ceballos-Diaz C, Cruz PE, Rosario AM, Lewis J, Giasson BI, Golde TE (2013) Conformational templating of alpha-synuclein aggregates in neuronal-glial cultures. Mol Neurodegener 8:17. doi: 10.1186/1750-1326-8-171750-1326-8-17
108. Young D, Mayer F, Vidotto N, Schweizer T, Berth R, Abramowski D, Shimshek DR, van der Putten PH, Schmid P (2013) Mutant huntingtin gene-dose impacts on aggregate deposition, DARPP32 expression and neuroinflammation in HdhQ150 mice. PLoS ONE 8(9):e75108. doi: 10.1371/journal.pone.0075108PONE-D-12-35261
109. Ben-Zvi A, Miller EA, Morimoto RI (2009) Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. P Natl Acad Sci USA 106(35):14914-14919. doi: 10.1073/pnas.0902882106
110. Nussbaum-Krammer CI, Morimoto RI (2014) Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases. Dis Models Mech 7(1):31-39. doi: 10.1242/Dmm.013011
111. Gitler AD, Lehmann R (2012) Modeling human disease. Science 337(6092):269. doi: 10.1126/science.1227179
112. Auluck PK, Caraveo G, Lindquist S (2010) Alpha-synuclein: membrane interactions and toxicity in Parkinson's disease. Annu Rev Cell Dev Biol 26:211-233. doi: 10.1146/annurev.cellbio.042308.113313
113. Eisbach SE, Outeiro TF (2013) Alpha-synuclein and intracellular trafficking: impact on the spreading of Parkinson's disease pathology. J Mol Med (Berl) 91(6):693-703. doi: 10.1007/s00109-013-1038-9
114. Tenreiro S, Reimao-Pinto MM, Antas P, Rino J, Wawrzycka D, Macedo D, Rosado-Ramos R, Amen T, Waiss M, Magalhaes F, Gomes A, Santos CN, Kaganovich D, Outeiro TF (2014) Phosphorylation modulates clearance of alpha-synuclein inclusions in a yeast model of Parkinson's disease. PLoS Genet 10(5):11-14. doi: 10.1371/journal.pgen.1004302
115. Outeiro TF, Lindquist S (2003) Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302(5651):1772-1775. doi: 10.1126/science.1090439
116. Nystrom T, Liu BD (2014) Protein quality control in time and space - links to cellular aging. FEMS Yeast Res 14(1):40-48. doi: 10.1111/1567-1364.12095
117. Nystrom T (2013) Aging: filtering out bad mitochondria. Curr Biol 23(23):R1037-R1039. doi: 10.1016/j.cub.2013.10.049
118. Nystrom T, Liu BD (2014) The mystery of aging and rejuvenation - a budding topic. Curr Opin Microbiol 18:61-67. doi: 10.1016/j.mib.2014.02.003
119. Clay L, Caudron F, Denoth-Lippuner A, Boettcher B, Frei SB, Snapp EL, Barral Y (2014) A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell. Elife 3:3-11. doi: 10.7554/eLife.01883
120. Lippuner AD, Julou T, Barral Y (2014) Budding yeast as a model organism to study the effects of age. FEMS Microbiol Rev 38(2):300-325. doi: 10.1111/1574-6976.12060
121. Lindner AB, Madden R, Dernarez A, Stewart EJ, Taddei F (2008) Asymmetric segregation of protein aggregates is associated with cellular aging and rejuvenation. P Natl Acad Sci USA 105(8):3076-3081. doi: 10.1073/pnas.0708931105
122. Coelho M, Dereli A, Haese A, Kuhn S, Malinovska L, DeSantis ME, Shorter J, Alberti S, Gross T, Tolic-Norrelykke IM (2013) Fission yeast does not age under favorable conditions, but does so after stress. Curr Biol 23(19):1844-1852. doi: 10.1016/j.cub.2013.07.084
123. Anderson P, Kedersha N (2006) RNA granules. Journal of Cell Biology 172(6):803-808. doi: 10.1083/jcb.200512082
124. Rujano MA, Bosveld F, Salomons FA, Dijk F, van Waarde MAWH, van der Want JJL, de Vos RAI, Brunt ER, Sibon OCM, Kampinga HH (2006) Polarised asymmetric inheritance of accumulated protein damage in higher eukaryotes. PLoS Biol 4(12):2325-2335. doi: 10.1371/journal.pbio.0040417
125. Bufalino MR, DeVeale B, van der Kooy D (2013) The asymmetric segregation of damaged proteins is stem cell-type dependent. J Cell Biol 201(4):523-530. doi: 10.1083/jcb.201207052
126. Fuentealba LC, Eivers E, Geissert D, Taelman V, De Robertis EM (2008) Asymmetric mitosis: unequal segregation of proteins destined for degradation. P Natl Acad Sci USA 105(22):7732-7737. doi: 10.1073/pnas.0803027105
127. Sinsimer KS, Lee JJ, Thiberge SY, Gavis ER (2013) Germ plasm anchoring is a dynamic state that requires persistent trafficking. Cell Rep 5(5):1169-1177. doi: 10.1016/j.celrep.2013.10.045
128. Erjavec N, Nystrom T (2007) Sir2p-dependent protein segregation gives rise to a superior reactive oxygen species management in the progeny of Saccharomyces cerevisiae. P Natl Acad Sci USA 104(26):10877-10881. doi: 10.1073/pnas.0701634104
129. Erjavec N, Cvijovic M, Klipp E, Nystrom T (2008) Selective benefits of damage partitioning in unicellular systems and its effects on aging. P Natl Acad Sci USA 105(48):18764-18769. doi: 10.1073/pnas.0804550105
130. Liu B, Larsson L, Franssens V, Hao X, Hill SM, Andersson V, Hoglund D, Song J, Yang X, Oling D, Grantham J, Winderickx J, Nystrom T (2011) Segregation of protein aggregates involves actin and the polarity machinery. Cell 147(5):959-961. doi: 10.1016/j.cell.2011.11.018
131. Li J, Li T, Zhang X, Tang Y, Yang J, Le W (2014) Human superoxide dismutase 1 overexpression in motor neurons of Caenorhabditis elegans causes axon guidance defect and neurodegeneration. Neurobiol Aging 35(4):837-846. doi: 10.1016/j.neurobiolaging.2013.09.003
132. Liu-Yesucevitz L, Bassell GJ, Gitler AD, Hart AC, Klann E, Richter JD, Warren ST, Wolozin B (2011) Local RNA translation at the synapse and in disease. J Neurosci 31(45):16086-16093. doi: 10.1523/Jneurosci.4105-11.2011
133. Sun Z, Diaz Z, Fang X, Hart MP, Chesi A, Shorter J, Gitler AD (2011) Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS. PLoS Biol 9(4):e1000614. doi: 10.1371/journal.pbio.1000614
134. Spokoini R, Shamir M, Keness A, Kaganovich D (2013) 4D imaging of protein aggregation in live cells. J Vis Exp 74:4-6. doi: 10.3791/50083
135. Shipley FB, Clark CM, Alkema MJ, Leifer AM (2014) Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans. Front Neural Circuits 8:28. doi: 10.3389/fncir.2014.00028
136. Baker SM, Buckheit RW 3rd, Falk MM (2010) Green-to-red photoconvertible fluorescent proteins: tracking cell and protein dynamics on standard wide-field mercury arc-based microscopes. BMC Cell Biol 11:15. doi: 10.1186/1471-2121-11-151471-2121-11-15