Article

You have full text access to this OnlineOpen article

A kinetic assessment of the C. elegans amyloid disaggregation activity enables uncoupling of disassembly and proteolysis

  1. Jan Bieschke1,†,§,
  2. Ehud Cohen2,‡,§,
  3. Amber Murray1,
  4. Andrew Dillin2,
  5. Jeffery W. Kelly1,*

Article first published online: 21 AUG 2009

DOI: 10.1002/pro.234

Issue

Protein Science

Protein Science

Volume 18, Issue 11, pages 2231–2241, November 2009

Additional Information

How to Cite

Bieschke, J., Cohen, E., Murray, A., Dillin, A. and Kelly, J. W. (2009), A kinetic assessment of the C. elegans amyloid disaggregation activity enables uncoupling of disassembly and proteolysis. Protein Science, 18: 2231–2241. doi: 10.1002/pro.234

Author Information

  1. 1

    Departments of Chemistry and Molecular and Experimental Medicine, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037

  2. 2

    The Howard Hughes Medical Institute and Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037

  1. †

    Max-Delbrück-Center for Molecular Medicine, Robert-Roessle-Str. 10, Berlin-Buch 13125, Germany

  2. ‡

    Institute of Medical Research Israel Canada (IMRIC), The Hebrew University of Jerusalem, Ein-Karem, Jerusalem 91121, Israel

  1. §

    †Jan Bieschke and Ehud Cohen contributed equally to this work.

*The Scripps Research Institute, BCC 265, 10550 N. Torrey Pines Road, La Jolla, CA 92037

Publication History

  1. Issue published online: 23 OCT 2009
  2. Article first published online: 21 AUG 2009
  3. Accepted manuscript online: 21 AUG 2009 12:00AM EST
  4. Manuscript Accepted: 13 AUG 2009
  5. Manuscript Received: 27 MAY 2009

Funded by

  • NGFNplus. Grant Number: 01GS08132
  • NIH. Grant Number: AG031097
  • The Bundy Foundation
  • Helmholz Gemeinschaft
  • Skaggs Institute for Chemical Biology
  • Lita Annenberg Hazen Foundation

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (685K)

References

  • 1
    Kelly JW ( 1998) The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr Opin Struct Biol 8: 101–106.
  • 2
    Dobson CM ( 2003) Protein folding and misfolding. Nature 426: 884–890.
  • 3
    Selkoe DJ ( 2004) Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nat Cell Biol 6: 1054–1061.
  • 4
    Sekijima Y, Wiseman RL, Matteson J, Hammarstrom P, Miller SR, Sawkar AR, Balch WE, Kelly JW ( 2005) The biological and chemical basis for tissue-selective amyloid disease. Cell 121: 73–85.
  • 5
    Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE ( 1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90: 549–558.
  • 6
    Bates G ( 2003) Huntingtin aggregation and toxicity in Huntington's disease. Lancet 361: 1642–1644.
  • 7
    Prusiner SB ( 1998) The prion diseases. Brain Pathol 8: 499–513.
  • 8
    Tanzi RE, Bertram L ( 2005) Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 120: 545–555.
  • 9
    Balch WE, Morimoto RI, Dillin A, Kelly JW ( 2008) Adapting proteostasis for disease intervention. Science 319: 916–919.
  • 10
    Cohen E, Dillin A ( 2008) The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat Rev Neurosci 9: 759–767.
  • 11
    Brignull HR, Morley JF, Morimoto RI ( 2007) The stress of misfolded proteins: C. elegans models for neurodegenerative disease and aging. Adv Exp Med Biol 594: 167–189.
  • 12
    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: 10417–10422.
  • 13
    Dillin A, Crawford DK, Kenyon C ( 2002) Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298: 830–834.
  • 14
    Amaducci L, Tesco G ( 1994) Aging as a major risk for degenerative diseases of the central nervous system. Curr Opin Neurol 7: 283–286.
  • 15
    Kenyon C ( 2005) The plasticity of aging: insights from long-lived mutants. Cell 120: 449–460.
  • 16
    Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P, Le Bouc Y ( 2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182–187.
  • 17
    Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P ( 2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105: 3438–3442.
  • 18
    Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD ( 2008) FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105: 13987–13992.
  • 19
    Hsu AL, Murphy CT, Kenyon C ( 2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300: 1142–1145.
  • 20
    Morley JF, Morimoto RI ( 2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15: 657–664.
  • 21
    Link CD ( 1995) Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci USA 92: 9368–9372.
  • 22
    Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A ( 2006) Opposing activities protect against age-onset proteotoxicity. Science 313: 1604–1610.
  • 23
    Chaudhuri TK, Paul S ( 2006) Protein-misfolding diseases and chaperone-based therapeutic approaches. FEBS J 273: 1331–1349.
  • 24
    Shorter J, Lindquist S ( 2004) Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304: 1793–1797.
  • 25
    Solomon B, Koppel R, Frankel D, Hanan-Aharon E ( 1997) Disaggregation of Alzheimer beta-amyloid by site-directed mAb. Proc Natl Acad Sci USA 94: 4109–4112.
  • 26
    Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P ( 1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400: 173–177.
  • 27
    Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, Sun X, Frosch MP, Selkoe DJ ( 2003) Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40: 1087–1093.
  • 28
    Powers ET, Powers DL ( 2006) The kinetics of nucleated polymerizations at high concentrations: amyloid fibril formation near and above the “supercritical concentration”. Biophys J 91: 122–132.
  • 29
    Bieschke J, Zhang Q, Powers ET, Lerner RA, Kelly JW ( 2005) Oxidative metabolites accelerate Alzheimer's amyloidogenesis by a two-step mechanism, eliminating the requirement for nucleation. Biochemistry 44: 4977–4983.
  • 30
    Levine H ( 1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309: 274–284.
  • 31
    Krebs MR, Bromley EH, Donald AM ( 2005) The binding of thioflavin-T to amyloid fibrils: localisation and implications. J Struct Biol 149: 30–37.
  • 32
    Klement K, Wieligmann K, Meinhardt J, Hortschansky P, Richter W, Fandrich M ( 2007) Effect of different salt ions on the propensity of aggregation and on the structure of Alzheimer's abeta(1–40) amyloid fibrils. J Mol Biol 373: 1321–1333.
  • 33
    Shorter J, Lindquist S ( 2006) Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities. Mol Cell 23: 425–438.
  • 34
    Parsell DA, Kowal AS, Singer MA, Lindquist S ( 1994) Protein disaggregation mediated by heat-shock protein Hsp104. Nature 372: 475–478.
  • 35
    Glover JR, Lindquist S ( 1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94: 73–82.
View Full Article with Supporting Information (HTML) Get PDF (685K)