Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress

Nature Communications

Volumn 4, Issue , 2013, Pages

  Leitman, Julia ^a   Ulrich Hartl, F ^b   Lederkremer, Gerardo Z ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

HUNTINGTIN; OLIGOMER; POLYGLUTAMINE; PROTEIN P97;

AGGREGATION; DISEASE PREVALENCE; GENE; INHIBITION; NEUROLOGY; TOXIC SUBSTANCE; TOXICITY;

ARTICLE; CELL INCLUSION; CONTROLLED STUDY; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; ENDOPLASMIC RETICULUM STRESS; ENZYME INHIBITION; GENE OVEREXPRESSION; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; MUTANT; NERVE CELL; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN AGGREGATION; PROTEIN DEGRADATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STRIATE CORTEX; UNFOLDED PROTEIN RESPONSE;

ANIMALS; CELL LINE; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION; GENE EXPRESSION REGULATION; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; MICE; NERVE TISSUE PROTEINS; PEPTIDES;

EID: 84887792874     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms3753     Document Type: Article

References (35)

1. Imarisio, S. et al. Huntington's disease: from pathology and genetics to potential therapies. Biochem. J. 412, 191-209 (2008). (Pubitemid 351758226)
2. Sakahira, H., Breuer, P., Hayer-Hartl, M. K. & Hartl, F. U. Molecular chaperones as modulators of polyglutamine protein aggregation and toxicity. Proc. Natl Acad. Sci. USA 99(Suppl 4): 16412-16418 (2002). (Pubitemid 35470987)
3. Schaffar, G. et al. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol. Cell 15, 95-105 (2004). (Pubitemid 38850222)
4. Bano, D., Zanetti, F., Mende, Y. & Nicotera, P. Neurodegenerative processes in Huntington's disease. Cell Death Dis. 2, e228 (2011).
5. Finkbeiner, S. & Mitra, S. The ubiquitin-proteasome pathway in Huntington's disease. ScientificWorldJournal 8, 421-433 (2008). (Pubitemid 351669770)
6. Ortega, Z., Diaz-Hernandez, M. & Lucas, J. J. Is the ubiquitin-proteasome system impaired in Huntington's disease? Cell Mol. Life Sci. 64, 2245-2257 (2007). (Pubitemid 47347963)
7. Duennwald, M. L. & Lindquist, S. Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity. Genes Dev. 22, 3308-3319 (2008).
8. Yang, H. et al. Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP. PLoS One 5, e8905 (2010).
9. Benyair, R., Ron, E. & Lederkremer, G. Z. Protein quality control, retention, and degradation at the endoplasmic reticulum. Int. Rev. Cell Mol. Biol. 292, 197-280 (2011).
10. Smith, M. H., Ploegh, H. L. & Weissman, J. S. Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science 334, 1086-1090 (2011).
11. Carnemolla, A. et al. Rrs1 is involved in endoplasmic reticulum stress response in Huntington disease. J. Biol. Chem. 284, 18167-18173 (2009).
12. Reijonen, S., Putkonen, N., Norremolle, A., Lindholm, D. & Korhonen, L. Inhibition of endoplasmic reticulum stress counteracts neuronal cell death and protein aggregation caused by N-terminal mutant huntingtin proteins. Exp. Cell Res. 314, 950-960 (2008).
13. Roussel, B. D. et al. Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol. 12, 105-118 (2013).
14. Vidal, R., Caballero, B., Couve, A. & Hetz, C. Converging pathways in the occurrence of endoplasmic reticulum (ER) stress in Huntington's disease. Curr. Mol. Med. 11, 1-12 (2011).
15. Lajoie, P. & Snapp, E. L. Formation and toxicity of soluble polyglutamine oligomers in living cells. PLoS One 5, e15245 (2010).
16. Takahashi, T. et al. Soluble polyglutamine oligomers formed prior to inclusion body formation are cytotoxic. Hum. Mol. Genet. 17, 345-356 (2008).
17. Mitra, S., Tsvetkov, A. S. & Finkbeiner, S. Single neuron ubiquitin-proteasome dynamics accompanying inclusion body formation in huntington disease. J. Biol. Chem. 284, 4398-4403 (2009).
18. Ortega, Z. et al. Acute polyglutamine expression in inducible mouse model unravels ubiquitin/proteasome system impairment and permanent recovery attributable to aggregate formation. J. Neurosci. 30, 3675-3688 (2010).
19. Kamhi-Nesher, S. et al. A novel quality control compartment derived from the endoplasmic reticulum. Mol. Biol. Cell 12, 1711-1723 (2001). (Pubitemid 33049724)
20. Tolchinsky, S., Yuk, M. H., Ayalon, M., Lodish, H. F. & Lederkremer, G. Z. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits. Role of a juxtamembrane pentapeptide. J. Biol. Chem. 271, 14496-14503 (1996).
21. Kondratyev, M., Avezov, E., Shenkman, M., Groisman, B. & Lederkremer, G. Z. PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress. Exp. Cell Res. 313, 3395-3407 (2007). (Pubitemid 47404548)
22. Walter, P. & Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081-1086 (2011).
23. Iwawaki, T., Akai, R., Kohno, K. & Miura, M. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat. Med. 10, 98-102 (2004). (Pubitemid 38524705)
24. Hirabayashi, M. et al. VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration. Cell Death Differ. 8, 977-984 (2001). (Pubitemid 32994648)
25. Hartl, F. U., Bracher, A. & Hayer-Hartl, M. Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332 (2011).
26. Hipp, M. S. et al. Indirect inhibition of 26S proteasome activity in a cellular model of Huntington's disease. J. Cell Biol. 196, 573-587 (2012).
27. Behrends, C. et al. Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. Mol. Cell 23, 887-897 (2006). (Pubitemid 44363048)
28. Choi, B. K. et al. Large alpha-synuclein oligomers inhibit neuronal SNAREmediated vesicle docking. Proc. Natl Acad. Sci. USA 110, 4087-4092 (2013).
29. Haass, C. & Selkoe, D. J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8, 101-112 (2007). (Pubitemid 46432529)
30. Matus, S., Glimcher, L. H. & Hetz, C. Protein folding stress in neurodegenerative diseases: a glimpse into the ER. Curr. Opin. Cell Biol. 23, 239-252 (2011).
31. Poksay, K. S. et al. Valosin-containing protein gene mutations: cellular phenotypes relevant to neurodegeneration. J. Mol. Neurosci. 44, 91-102 (2011).
32. Ron, E. et al. Bypass of glycan-dependent glycoprotein delivery to ERAD by upregulated EDEM1. Mol. Biol. Cell 22, 3945-3954 (2011).
33. Trettel, F. et al. Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells. Hum. Mol. Genet. 9, 2799-2809 (2000).
34. Hackam, A. S. et al. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J. Cell Biol. 141, 1097-1105 (1998). (Pubitemid 28265605)
35. Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506 (1996). (Pubitemid 26374323)