Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Saccharomyces cerevisiae

REFERENCES

• de la Monte SM, Vonsattel JP, Richardson EP, Jr. 1988. Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington’s disease. J Neuropathol Exp Neurol 47:516–525. https://doi.org/10.1097/00005072-198809000-00003.
   PubMed Web of Science ®Google Scholar
• Fennema-Notestine C, Archibald SL, Jacobson MW, Corey-Bloom J, Paulsen JS, Peavy GM, Gamst AC, Hamilton JM, Salmon DP, Jernigan TL. 2004. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease. Neurology 63:989–995. https://doi.org/10.1212/01.wnl.0000138434.68093.67.
   PubMed Web of Science ®Google Scholar
• Jayaraman M, Kodali R, Sahoo B, Thakur AK, Mayasundari A, Mishra R, Peterson CB, Wetzel R. 2012. Slow amyloid nucleation via alpha-helix-rich oligomeric intermediates in short polyglutamine-containing huntingtin fragments. J Mol Biol 415:881–899. https://doi.org/10.1016/j.jmb.2011.12.010.
   PubMed Web of Science ®Google Scholar
• Landrum E, Wetzel R. 2014. Biophysical underpinnings of the repeat length dependence of polyglutamine amyloid formation. J Biol Chem 289:10254–10260. https://doi.org/10.1074/jbc.C114.552943.
   PubMed Web of Science ®Google Scholar
• Finkbeiner S. 2011. Huntington’s disease. Cold Spring Harb Perspect Biol 3:a007476. https://doi.org/10.1101/cshperspect.a007476.
   PubMed Web of Science ®Google Scholar
• Arndt JR, Chaibva M, Legleiter J. 2015. The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease. Biomol Concepts 6:33–46. https://doi.org/10.1515/bmc-2015-0001.
   PubMedGoogle Scholar
• Pandey NK, Isas JM, Rawat A, Lee RV, Langen J, Pandey P, Langen R. 2018. The 17-residue-long N terminus in huntingtin controls stepwise aggregation in solution and on membranes via different mechanisms. J Biol Chem 293:2597–2605. https://doi.org/10.1074/jbc.M117.813667.
   PubMed Web of Science ®Google Scholar
• Crick SL, Ruff KM, Garai K, Frieden C, Pappu RV. 2013. Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation. Proc Natl Acad Sci USA 110:20075–20080. https://doi.org/10.1073/pnas.1320626110.
   PubMed Web of Science ®Google Scholar
• Sivanandam VN, Jayaraman M, Hoop CL, Kodali R, Wetzel R, van der Wel PC. 2011. The aggregation-enhancing huntingtin N-terminus is helical in amyloid fibrils. J Am Chem Soc 133:4558–4566. https://doi.org/10.1021/ja110715f.
   PubMed Web of Science ®Google Scholar
• Khoshnan A, Ko J, Patterson PH. 2002. Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity. Proc Natl Acad Sci USA 99:1002–1007. https://doi.org/10.1073/pnas.022631799.
   PubMed Web of Science ®Google Scholar
• Chen M, Wolynes PG. 2017. Aggregation landscapes of huntingtin exon 1 protein fragments and the critical repeat length for the onset of Huntington’s disease. Proc Natl Acad Sci USA 114:4406–4411. https://doi.org/10.1073/pnas.1702237114.
   PubMed Web of Science ®Google Scholar
• Bhattacharyya A, Thakur AK, Chellgren VM, Thiagarajan G, Williams AD, Chellgren BW, Creamer TP, Wetzel R. 2006. Oligoproline effects on polyglutamine conformation and aggregation. J Mol Biol 355:524–535. https://doi.org/10.1016/j.jmb.2005.10.053.
   PubMed Web of Science ®Google Scholar
• Darnell G, Orgel JP, Pahl R, Meredith SC. 2007. Flanking polyproline sequences inhibit beta-sheet structure in polyglutamine segments by inducing PPII-like helix structure. J Mol Biol 374:688–704. https://doi.org/10.1016/j.jmb.2007.09.023.
   PubMed Web of Science ®Google Scholar
• Slepko N, Bhattacharyya AM, Jackson GR, Steffan JS, Marsh JL, Thompson LM, Wetzel R. 2006. Normal-repeat-length polyglutamine peptides accelerate aggregation nucleation and cytotoxicity of expanded polyglutamine proteins. Proc Natl Acad Sci USA 103:14367–14372. https://doi.org/10.1073/pnas.0602348103.
   PubMed Web of Science ®Google Scholar
• Rubinsztein DC. 2002. Lessons from animal models of Huntington’s disease. Trends Genet 18:202–209. https://doi.org/10.1016/S0168-9525(01)02625-7.
   PubMed Web of Science ®Google Scholar
• Heintz N, Zoghbi HY. 2000. Insights from mouse models into the molecular basis of neurodegeneration. Annu Rev Physiol 62:779–802. https://doi.org/10.1146/annurev.physiol.62.1.779.
   PubMed Web of Science ®Google Scholar
• Li SH, Li XJ. 2004. Huntingtin and its role in neuronal degeneration. Neuroscientist 10:467–475. https://doi.org/10.1177/1073858404266777.
   PubMed Web of Science ®Google Scholar
• Labbadia J, Morimoto RI. 2013. Huntington’s disease: underlying molecular mechanisms and emerging concepts. Trends Biochem Sci 38:378–385. https://doi.org/10.1016/j.tibs.2013.05.003.
   PubMed Web of Science ®Google Scholar
• Sherman MY, Muchowski PJ. 2003. Making yeast tremble: yeast models as tools to study neurodegenerative disorders. Neuromolecular Med 4:133–146. https://doi.org/10.1385/NMM:4:1-2:133.
   PubMed Web of Science ®Google Scholar
• Khurana V, Lindquist S. 2010. Modelling neurodegeneration in Saccharomyces cerevisiae: why cook with baker’s yeast? Nat Rev Neurosci 11:436–449. https://doi.org/10.1038/nrn2809.
   PubMed Web of Science ®Google Scholar
• Mason RP, Giorgini F. 2011. Modeling Huntington disease in yeast: perspectives and future directions. Prion 5:269–276. https://doi.org/10.4161/pri.18005.
   PubMed Web of Science ®Google Scholar
• Meriin AB, Zhang X, He X, Newnam GP, Chernoff YO, Sherman MY. 2002. Huntingtin toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J Cell Biol 157:997–1004. https://doi.org/10.1083/jcb.200112104.
   PubMed Web of Science ®Google Scholar
• Duennwald ML, Jagadish S, Muchowski PJ, Lindquist S. 2006. Flanking sequences profoundly alter polyglutamine toxicity in yeast. Proc Natl Acad Sci USA 103:11045–11050. https://doi.org/10.1073/pnas.0604547103.
   PubMed Web of Science ®Google Scholar
• Gokhale KC, Newnam GP, Sherman MY, Chernoff YO. 2005. Modulation of prion-dependent polyglutamine aggregation and toxicity by chaperone proteins in the yeast model. J Biol Chem 280:22809–22818. https://doi.org/10.1074/jbc.M500390200.
   PubMed Web of Science ®Google Scholar
• Osherovich LZ, Cox BS, Tuite MF, Weissman JS. 2004. Dissection and design of yeast prions. PLoS Biol 2:E86. https://doi.org/10.1371/journal.pbio.0020086.
   PubMed Web of Science ®Google Scholar
• Duennwald ML, Jagadish S, Giorgini F, Muchowski PJ, Lindquist S. 2006. A network of protein interactions determines polyglutamine toxicity. Proc Natl Acad Sci USA 103:11051–11056. https://doi.org/10.1073/pnas.0604548103.
   PubMed Web of Science ®Google Scholar
• Derkatch IL, Uptain SM, Outeiro TF, Krishnan R, Lindquist SL, Liebman SW. 2004. Effects of Q/N-rich, polyQ, and non-polyQ amyloids on the de novo formation of the [PSI+] prion in yeast and aggregation of Sup35 in vitro. Proc Natl Acad Sci USA 101:12934–12939. https://doi.org/10.1073/pnas.0404968101.
   PubMed Web of Science ®Google Scholar
• Urakov VN, Vishnevskaya AB, Alexandrov IM, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD. 2010. Interdependence of amyloid formation in yeast: implications for polyglutamine disorders and biological functions. Prion 4:45–52. https://doi.org/10.4161/pri.4.1.11074.
   PubMed Web of Science ®Google Scholar
• Alexandrov IM, Vishnevskaya AB, Ter-Avanesyan MD, Kushnirov VV. 2008. Appearance and propagation of polyglutamine-based amyloids in yeast: tyrosine residues enable polymer fragmentation. J Biol Chem 283:15185–15192. https://doi.org/10.1074/jbc.M802071200.
   PubMed Web of Science ®Google Scholar
• Wang Y, Meriin AB, Zaarur N, Romanova NV, Chernoff YO, Costello CE, Sherman MY. 2009. Abnormal proteins can form aggresome in yeast: aggresome-targeting signals and components of the machinery. FASEB J 23:451–463. https://doi.org/10.1096/fj.08-117614.
   PubMed Web of Science ®Google Scholar
• Aktar F, Burudpakdee C, Polanco M, Pei S, Swayne TC, Lipke PN, Emtage L. 2019. The huntingtin inclusion is a dynamic phase-separated compartment. Life Sci Alliance 2:e201900489. https://doi.org/10.26508/lsa.201900489.
   Google Scholar
• Zhao X, Park YN, Todor H, Moomau C, Masison D, Eisenberg E, Greene LE. 2012. Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast. J Biol Chem 287:23346–23355. https://doi.org/10.1074/jbc.M111.287748.
   PubMed Web of Science ®Google Scholar
• Gong H, Romanova NV, Allen KD, Chandramowlishwaran P, Gokhale K, Newnam GP, Mieczkowski P, Sherman MY, Chernoff YO. 2012. Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast. PLoS Genet 8:e1002634. https://doi.org/10.1371/journal.pgen.1002634.
   Google Scholar
• Kochneva-Pervukhova NV, Alexandrov AI, Ter-Avanesyan MD. 2012. Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast. PLoS One 7:e29832. https://doi.org/10.1371/journal.pone.0029832.
   Google Scholar
• Peng B, Williams TC, Henry M, Nielsen LK, Vickers CE. 2015. Controlling heterologous gene expression in yeast cell factories on different carbon substrates and across the diauxic shift: a comparison of yeast promoter activities. Microb Cell Fact 14:91. https://doi.org/10.1186/s12934-015-0278-5.
   PubMed Web of Science ®Google Scholar
• Lin HK, Boatz JC, Krabbendam IE, Kodali R, Hou Z, Wetzel R, Dolga AM, Poirier MA, van der Wel PCA. 2017. Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core. Nat Commun 8:15462. https://doi.org/10.1038/ncomms15462.
   PubMed Web of Science ®Google Scholar
• Lum R, Tkach JM, Vierling E, Glover JR. 2004. Evidence for an unfolding/threading mechanism for protein disaggregation by Saccharomyces cerevisiae Hsp104. J Biol Chem 279:29139–29146. https://doi.org/10.1074/jbc.M403777200.
   PubMed Web of Science ®Google Scholar
• Hung GC, Masison DC. 2006. N-terminal domain of yeast Hsp104 chaperone is dispensable for thermotolerance and prion propagation but necessary for curing prions by Hsp104 overexpression. Genetics 173:611–620. https://doi.org/10.1534/genetics.106.056820.
   PubMed Web of Science ®Google Scholar
• Wanker EE, Scherzinger E, Heiser V, Sittler A, Eickhoff H, Lehrach H. 1999. Membrane filter assay for detection of amyloid-like polyglutamine-containing protein aggregates. Methods Enzymol 309:375–386. https://doi.org/10.1016/s0076-6879(99)09026-6.
   PubMed Web of Science ®Google Scholar
• Ast A, Schindler F, Buntru A, Schnoegl S, Wanker EE. 2018. A filter retardation assay facilitates the detection and quantification of heat-stable, amyloidogenic mutant huntingtin aggregates in complex biosamples. Methods Mol Biol 1780:31–40. https://doi.org/10.1007/978-1-4939-7825-0_3.
   PubMedGoogle Scholar
• Muchowski PJ, Schaffar G, Sittler A, Wanker EE, Hayer-Hartl MK, Hartl FU. 2000. Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc Natl Acad Sci USA 97:7841–7846. https://doi.org/10.1073/pnas.140202897.
   PubMed Web of Science ®Google Scholar
• 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 105:6439–6444. https://doi.org/10.1073/pnas.0802082105.
   PubMed Web of Science ®Google Scholar
• Kryndushkin D, Wickner RB, Shewmaker F. 2011. FUS/TLS forms cytoplasmic aggregates, inhibits cell growth and interacts with TDP-43 in a yeast model of amyotrophic lateral sclerosis. Protein Cell 2:223–236. https://doi.org/10.1007/s13238-011-1525-0.
   PubMed Web of Science ®Google Scholar
• Bauerlein FJB, Saha I, Mishra A, Kalemanov M, Martinez-Sanchez A, Klein R, Dudanova I, Hipp MS, Hartl FU, Baumeister W, Fernandez-Busnadiego R. 2017. In situ architecture and cellular interactions of polyQ inclusions. Cell 171:179–187.e10. https://doi.org/10.1016/j.cell.2017.08.009.
   PubMed Web of Science ®Google Scholar
• Sin O, Mata-Cabana A, Seinstra RI, Nollen EAA. 2018. Filter retardation assay for detecting and quantifying polyglutamine aggregates using Caenorhabditis elegans lysates. Bio Protoc 8:e3042. https://doi.org/10.21769/BioProtoc.3042.
   Google Scholar
• 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. https://doi.org/10.1091/mbc.12.5.1393.
   PubMed Web of Science ®Google Scholar
• Ast A, Buntru A, Schindler F, Hasenkopf R, Schulz A, Brusendorf L, Klockmeier K, Grelle G, McMahon B, Niederlechner H, Jansen I, Diez L, Edel J, Boeddrich A, Franklin SA, Baldo B, Schnoegl S, Kunz S, Purfurst B, Gaertner A, Kampinga HH, Morton AJ, Petersen A, Kirstein J, Bates GP, Wanker EE. 2018. mHTT seeding activity: a marker of disease progression and neurotoxicity in models of Huntington’s disease. Mol Cell 71:675–688.e6. https://doi.org/10.1016/j.molcel.2018.07.032.
   PubMed Web of Science ®Google Scholar
• Hazeki N, Tukamoto T, Goto J, Kanazawa I. 2000. Formic acid dissolves aggregates of an N-terminal huntingtin fragment containing an expanded polyglutamine tract: applying to quantification of protein components of the aggregates. Biochem Biophys Res Commun 277:386–393. https://doi.org/10.1006/bbrc.2000.3682.
   PubMed Web of Science ®Google Scholar
• Glover JR, Lindquist S. 1998. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94:73–82. https://doi.org/10.1016/s0092-8674(00)81223-4.
   PubMed Web of Science ®Google Scholar
• Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR. 2017. Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science 357:273–279. https://doi.org/10.1126/science.aan1052.
   PubMed Web of Science ®Google Scholar
• Parsell DA, Kowal AS, Singer MA, Lindquist S. 1994. Protein disaggregation mediated by heat-shock protein Hsp104. Nature 372:475–478. https://doi.org/10.1038/372475a0.
   PubMed Web of Science ®Google Scholar
• 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 151:778–793. https://doi.org/10.1016/j.cell.2012.09.038.
   PubMed Web of Science ®Google Scholar
• Jackrel ME, DeSantis ME, Martinez BA, Castellano LM, Stewart RM, Caldwell KA, Caldwell GA, Shorter J. 2014. Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events. Cell 156:170–182. https://doi.org/10.1016/j.cell.2013.11.047.
   PubMed Web of Science ®Google Scholar
• Vacher C, Garcia-Oroz L, Rubinsztein DC. 2005. Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington’s disease. Hum Mol Genet 14:3425–3433. https://doi.org/10.1093/hmg/ddi372.
   PubMed Web of Science ®Google Scholar
• Perrin V, Regulier E, Abbas-Terki T, Hassig R, Brouillet E, Aebischer P, Luthi-Carter R, Deglon N. 2007. Neuroprotection by Hsp104 and Hsp27 in lentiviral-based rat models of Huntington’s disease. Mol Ther 15:903–911. https://doi.org/10.1038/mt.sj.6300141.
   PubMed Web of Science ®Google Scholar
• Carmichael J, Chatellier J, Woolfson A, Milstein C, Fersht AR, Rubinsztein DC. 2000. Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington’s disease. Proc Natl Acad Sci USA 97:9701–9705. https://doi.org/10.1073/pnas.170280697.
   PubMed Web of Science ®Google Scholar
• Satyal SH, Schmidt E, Kitagawa K, Sondheimer N, Lindquist S, Kramer JM, Morimoto RI. 2000. Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci USA 97:5750–5755. https://doi.org/10.1073/pnas.100107297.
   PubMed Web of Science ®Google Scholar
• Cushman-Nick M, Bonini NM, Shorter J. 2013. Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model. PLoS Genet 9:e1003781. https://doi.org/10.1371/journal.pgen.1003781.
   PubMed Web of Science ®Google Scholar
• Dehay B, Bertolotti A. 2006. Critical role of the proline-rich region in huntingtin for aggregation and cytotoxicity in yeast. J Biol Chem 281:35608–35615. https://doi.org/10.1074/jbc.M605558200.
   PubMed Web of Science ®Google Scholar
• Cox B, Ness F, Tuite M. 2003. Analysis of the generation and segregation of propagons: entities that propagate the [PSI+] prion in yeast. Genetics 165:23–33. https://doi.org/10.1093/genetics/165.1.23.
   PubMed Web of Science ®Google Scholar
• Peskett TR, Rau F, O’Driscoll J, Patani R, Lowe AR, Saibil HR. 2018. A liquid to solid phase transition underlying pathological huntingtin exon1 aggregation. Mol Cell 70:588–601.e6. https://doi.org/10.1016/j.molcel.2018.04.007.
   PubMed Web of Science ®Google Scholar
• Capitini C, Conti S, Perni M, Guidi F, Cascella R, De Poli A, Penco A, Relini A, Cecchi C, Chiti F. 2014. TDP-43 inclusion bodies formed in bacteria are structurally amorphous, non-amyloid and inherently toxic to neuroblastoma cells. PLoS One 9:e86720. https://doi.org/10.1371/journal.pone.0086720.
   PubMed Web of Science ®Google Scholar
• 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. https://doi.org/10.1016/j.cell.2015.07.047.
   PubMed Web of Science ®Google Scholar
• Sahl SJ, Weiss LE, Duim WC, Frydman J, Moerner WE. 2012. Cellular inclusion bodies of mutant huntingtin exon 1 obscure small fibrillar aggregate species. Sci Rep 2:895. https://doi.org/10.1038/srep00895.
   PubMed Web of Science ®Google Scholar
• Jung G, Masison DC. 2001. Guanidine hydrochloride inhibits Hsp104 activity in vivo: a possible explanation for its effect in curing yeast prions. Curr Microbiol 43:7–10. https://doi.org/10.1007/s002840010251.
   PubMed Web of Science ®Google Scholar
• Houser JR, Ford E, Chatterjea SM, Maleri S, Elston TC, Errede B. 2012. An improved short-lived fluorescent protein transcriptional reporter for Saccharomyces cerevisiae. Yeast 29:519–530. https://doi.org/10.1002/yea.2932.
   PubMed Web of Science ®Google Scholar
• Meriin AB, Zhang X, Alexandrov IM, Salnikova AB, Ter-Avanesian MD, Chernoff YO, Sherman MY. 2007. Endocytosis machinery is involved in aggregation of proteins with expanded polyglutamine domains. FASEB J 21:1915–1925. https://doi.org/10.1096/fj.06-6878com.
   PubMed Web of Science ®Google Scholar
• Zhao X, Rodriguez R, Silberman RE, Ahearn JM, Saidha S, Cummins KC, Eisenberg E, Greene LE. 2017. Heat shock protein 104 (Hsp104)-mediated curing of [PSI(+)] yeast prions depends on both [PSI(+)] conformation and the properties of the Hsp104 homologs. J Biol Chem 292:8630–8641. https://doi.org/10.1074/jbc.M116.770719.
   PubMed Web of Science ®Google Scholar
• Sherman F. 2002. Getting started with yeast. Methods Enzymol 350:3–41. https://doi.org/10.1016/s0076-6879(02)50954-x.
   PubMed Web of Science ®Google Scholar