The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model

Molecular Cell

Volumn 62, Issue 2, 2016, Pages 272-283

  Kakkar, Vaishali ^a   Månsson, Cecilia ^b   de Mattos, Eduardo P ^a,c   Bergink, Steven ^a   van der Zwaag, Marianne ^a   van Waarde, Maria A W H ^a   Kloosterhuis, Niels J ^a   Melki, Ronald ^d   van Cruchten, Remco T P ^b   Al Karadaghi, Salam ^b   Arosio, Paolo ^e   Dobson, Christopher M ^e   Knowles, Tuomas P J ^e   Bates, Gillian P ^f   van Deursen, Jan M ^g   Linse, Sara ^b   van de Sluis, Bart ^a   Emanuelsson, Cecilia ^b   Kampinga, Harm H ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b LUND UNIVERSITY   (Sweden)

^c FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^d CNRS   (France)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f KING'S COLLEGE LONDON   (United Kingdom)

^g MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; CHAPERONE; DNAJB6; HYDROXYL GROUP; POLYGLUTAMINE; PROTEIN DNAJ; SERINE; THREONINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; FEMALE; GENETIC VARIABILITY; HUMAN; HUMAN CELL; IN VITRO STUDY; LIFESPAN; MALE; MOUSE; NERVE CELL; NEURITE; NONHUMAN; PATHOGENESIS; PROTEIN AGGREGATION; PROTEIN INTERACTION; PROTEIN MOTIF; STOICHIOMETRY;

EID: 84963566241     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2016.03.017     Document Type: Article

References (56)

1. Akerfelt M., Morimoto R.I., Sistonen L. Heat shock factors: integrators of cell stress, development and lifespan. Nat. Rev. Mol. Cell Biol. 2010, 11:545-555.
2. Arosio P., Vendruscolo M., Dobson C.M., Knowles T.P.J. Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends Pharmacol. Sci. 2014, 35:127-135.
3. Bailey C.K., Andriola I.F.M., Kampinga H.H., Merry D.E. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2002, 11:515-523.
4. Carra S., Seguin S.J., Landry J. HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy. Autophagy 2008, 4:237-239.
5. Chan H.Y., Warrick J.M., Gray-Board G.L., Paulson H.L., Bonini N.M. Mechanisms of chaperone suppression of polyglutamine disease: selectivity, synergy and modulation of protein solubility in Drosophila. Hum. Mol. Genet. 2000, 9:2811-2820.
6. Chiti F., Dobson C.M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 2006, 75:333-366.
7. Cohen S.I.A., Vendruscolo M., Welland M.E., Dobson C.M., Terentjev E.M., Knowles T.P.J. Nucleated polymerization with secondary pathways. I. Time evolution of the principal moments. J. Chem. Phys. 2011, 135:065105.
8. Cohen S.I.A., Arosio P., Presto J., Kurudenkandy F.R., Biverstål H., Dolfe L., Dunning C., Yang X., Frohm B., Vendruscolo M., et al. A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers. Nat. Struct. Mol. Biol. 2015, 22:207-213.
9. Crippa V., Sau D., Rusmini P., Boncoraglio A., Onesto E., Bolzoni E., Galbiati M., Fontana E., Marino M., Carra S., et al. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum. Mol. Genet. 2010, 19:3440-3456.
10. Dai C., Whitesell L., Rogers A.B., Lindquist S. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 2007, 130:1005-1018.
11. Ehrnhoefer D.E., Duennwald M., Markovic P., Wacker J.L., Engemann S., Roark M., Legleiter J., Marsh J.L., Thompson L.M., Lindquist S., et al. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum. Mol. Genet. 2006, 15:2743-2751.
12. Ellerby L.M., Hackam A.S., Propp S.S., Ellerby H.M., Rabizadeh S., Cashman N.R., Trifiro M.A., Pinsky L., Wellington C.L., Salvesen G.S., et al. Kennedy's disease: caspase cleavage of the androgen receptor is a crucial event in cytotoxicity. J. Neurochem. 1999, 72:185-195.
13. Fujikake N., Nagai Y., Popiel H.A., Okamoto Y., Yamaguchi M., Toda T. Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J. Biol. Chem. 2008, 283:26188-26197.
14. Gillis J., Schipper-Krom S., Juenemann K., Gruber A., Coolen S., van den Nieuwendijk R., van Veen H., Overkleeft H., Goedhart J., Kampinga H.H., Reits E.A. The DNAJB6 and DNAJB8 protein chaperones prevent intracellular aggregation of polyglutamine peptides. J. Biol. Chem. 2013, 288:17225-17237.
15. Graham R.K., Deng Y., Slow E.J., Haigh B., Bissada N., Lu G., Pearson J., Shehadeh J., Bertram L., Murphy Z., et al. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 2006, 125:1179-1191.
16. Gunawardena S., Her L.S., Brusch R.G., Laymon R.A., Niesman I.R., Gordesky-Gold B., Sintasath L., Bonini N.M., Goldstein L.S. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 2003, 40:25-40.
17. Gusella J.F., MacDonald M.E. Molecular genetics: unmasking polyglutamine triggers in neurodegenerative disease. Nat. Rev. Neurosci. 2000, 1:109-115.
18. Haacke A., Broadley S.A., Boteva R., Tzvetkov N., Hartl F.U., Breuer P. Proteolytic cleavage of polyglutamine-expanded ataxin-3 is critical for aggregation and sequestration of non-expanded ataxin-3. Hum. Mol. Genet. 2006, 15:555-568.
19. Hageman J., Rujano M.A., van Waarde M.A.W.H., Kakkar V., Dirks R.P., Govorukhina N., Oosterveld-Hut H.M.J., Lubsen N.H., Kampinga H.H. A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol. Cell 2010, 37:355-369.
20. Hansson O., Nylandsted J., Castilho R.F., Leist M., Jäättelä M., Brundin P. Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression. Brain Res. 2003, 970:47-57.
21. Harms M.B., Sommerville R.B., Allred P., Bell S., Ma D., Cooper P., Lopate G., Pestronk A., Weihl C.C., Baloh R.H. Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Ann. Neurol. 2012, 71:407-416.
22. Hay D.G., Sathasivam K., Tobaben S., Stahl B., Marber M., Mestril R., Mahal A., Smith D.L., Woodman B., Bates G.P. Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach. Hum. Mol. Genet. 2004, 13:1389-1405.
23. Hipp M.S., Park S.H., Hartl F.U. Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol. 2014, 24:506-514.
24. Hoop C.L., Lin H.-K., Kar K., Hou Z., Poirier M.A., Wetzel R., van der Wel P.C.A. Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state nuclear magnetic resonance. Biochemistry 2014, 53:6653-6666.
25. Hoop C.L., Lin H.K., Kar K., Magyarfalvi G., Lamley J.M., Boatz J.C., Mandal A., Lewandowski J.R., Wetzel R., van der Wel P.C. Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core. Proc. Natl. Acad. Sci. USA 2016, 113:1546-1551.
26. Hunter P.J., Swanson B.J., Haendel M.A., Lyons G.E., Cross J.C. Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. Development 1999, 126:1247-1258.
27. Izawa I., Nishizawa M., Ohtakara K., Ohtsuka K., Inada H., Inagaki M. Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein. J. Biol. Chem. 2000, 275:34521-34527.
28. Kampinga H.H., Craig E.A. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat. Rev. Mol. Cell Biol. 2010, 11:579-592.
29. Kar K., Hoop C.L., Drombosky K.W., Baker M.A., Kodali R., Arduini I., van der Wel P.C.A., Horne W.S., Wetzel R. β-hairpin-mediated nucleation of polyglutamine amyloid formation. J. Mol. Biol. 2013, 425:1183-1197.
30. Knowles T.P.J., Vendruscolo M., Dobson C.M. The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 2014, 15:384-396.
31. Koch P., Breuer P., Peitz M., Jungverdorben J., Kesavan J., Poppe D., Doerr J., Ladewig J., Mertens J., Tüting T., et al. Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. Nature 2011, 480:543-546.
32. Labbadia J., Cunliffe H., Weiss A., Katsyuba E., Sathasivam K., Seredenina T., Woodman B., Moussaoui S., Frentzel S., Luthi-Carter R., et al. Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J. Clin. Invest. 2011, 121:3306-3319.
33. Månsson C., Kakkar V., Monsellier E., Sourigues Y., Härmark J., Kampinga H.H., Melki R., Emanuelsson C. DNAJB6 is a peptide-binding chaperone which can suppress amyloid fibrillation of polyglutamine peptides at substoichiometric molar ratios. Cell Stress Chaperones 2014, 19:227-239.
34. Månsson C., Arosio P., Hussein R., Kampinga H.H., Hashem R.M., Boelens W.C., Dobson C.M., Knowles T.P.J., Linse S., Emanuelsson C. Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Aβ42) aggregates leads to sub-stoichiometric inhibition of amyloid formation. J. Biol. Chem. 2014, 289:31066-31076.
35. Neef D.W., Turski M.L., Thiele D.J. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol. 2010, 8:e1000291.
36. Park S.-H., Kukushkin Y., Gupta R., Chen T., Konagai A., Hipp M.S., Hayer-Hartl M., Hartl F.U. PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell 2013, 154:134-145.
37. Popiel H.A., Takeuchi T., Fujita H., Yamamoto K., Ito C., Yamane H., Muramatsu S., Toda T., Wada K., Nagai Y. Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism. PLoS ONE 2012, 7:e51069.
38. Ramani B., Harris G.M., Huang R., Seki T., Murphy G.G., Costa Mdo.C., Fischer S., Saunders T.L., Xia G., McEachin R.C., Paulson H.L. A knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript. Hum. Mol. Genet. 2015, 24:1211-1224.
39. Raspe M., Gillis J., Krol H., Krom S., Bosch K., van Veen H., Reits E. Mimicking proteasomal release of polyglutamine peptides initiates aggregation and toxicity. J. Cell Sci. 2009, 122:3262-3271.
40. Ren P.-H., Lauckner J.E., Kachirskaia I., Heuser J.E., Melki R., Kopito R.R. Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates. Nat. Cell Biol. 2009, 11:219-225.
41. Ribchester R.R., Thomson D., Wood N.I., Hinks T., Gillingwater T.H., Wishart T.M., Court F.A., Morton A.J. Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington's disease mutation. Eur. J. Neurosci. 2004, 20:3092-3114.
42. Sarparanta J., Jonson P.H., Golzio C., Sandell S., Luque H., Screen M., McDonald K., Stajich J.M., Mahjneh I., Vihola A., et al. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat. Genet. 2012, 44:450-455. S1-S2.
43. Sathasivam K., Hobbs C., Turmaine M., Mangiarini L., Mahal A., Bertaux F., Wanker E.E., Doherty P., Davies S.W., Bates G.P. Formation of polyglutamine inclusions in non-CNS tissue. Hum. Mol. Genet. 1999, 8:813-822.
44. Sathasivam K., Neueder A., Gipson T.A., Landles C., Benjamin A.C., Bondulich M.K., Smith D.L., Faull R.L.M., Roos R.A.C., Howland D., et al. Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease. Proc. Natl. Acad. Sci. USA 2013, 110:2366-2370.
45. Seidel K., Meister M., Dugbartey G.J., Zijlstra M.P., Vinet J., Brunt E.R.P., van Leeuwen F.W., Rüb U., Kampinga H.H., den Dunnen W.F.A. Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type 3 (SCA3). Neuropathol. Appl. Neurobiol. 2012, 38:548-558.
46. Suarez-Cedeno G., Winder T., Milone M. DNAJB6 myopathy: a vacuolar myopathy with childhood onset. Muscle Nerve 2014, 49:607-610.
47. Suhr S.T., Senut M.C., Whitelegge J.P., Faull K.F., Cuizon D.B., Gage F.H. Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. J. Cell Biol. 2001, 153:283-294.
48. van Ree J., Zhou W., Li M., van Deursen J.M. Transgenesis in mouse embryonic stem cells. Methods Mol. Biol. 2011, 693:143-162.
49. Venkatraman P., Wetzel R., Tanaka M., Nukina N., Goldberg A.L. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 2004, 14:95-104.
50. Villella V.R., Esposito S., Bruscia E.M., Maiuri M.C., Raia V., Kroemer G., Maiuri L. Targeting the intracellular environment in cystic fibrosis: restoring autophagy as a novel strategy to circumvent the CFTR defect. Front. Pharmacol. 2013, 4:1.
51. Warrick J.M., Chan H.Y., Gray-Board G.L., Chai Y., Paulson H.L., Bonini N.M. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 1999, 23:425-428.
52. Watson E.D., Geary-Joo C., Hughes M., Cross J.C. The Mrj co-chaperone mediates keratin turnover and prevents the formation of toxic inclusion bodies in trophoblast cells of the placenta. Development 2007, 134:1809-1817.
53. Westermark P., Andersson A., Westermark G.T. Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol. Rev. 2011, 91:795-826.
54. Willander H., Presto J., Askarieh G., Biverstål H., Frohm B., Knight S.D., Johansson J., Linse S. BRICHOS domains efficiently delay fibrillation of amyloid β-peptide. J. Biol. Chem. 2012, 287:31608-31617.
55. Zoghbi H.Y., Orr H.T. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 2000, 23:217-247.
56. Zourlidou A., Gidalevitz T., Kristiansen M., Landles C., Woodman B., Wells D.J., Latchman D.S., de Belleroche J., Tabrizi S.J., Morimoto R.I., Bates G.P. Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation. Hum. Mol. Genet. 2007, 16:1078-1090.