DNAJ proteins and protein aggregation diseases

Current Topics in Medicinal Chemistry

Volumn 12, Issue 22, 2012, Pages 2479-2490

  Kakkar, Vaishali ^a   Prins, Louis C B ^a   Kampinga, Harm H ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Chaperonopathies; DNAJ proteins; Hsp70; Neurodegeneration; Protein aggregation diseases; Protein quality control

Indexed keywords

ANDROGEN RECEPTOR; ATAXIN 1; ATAXIN 3; CHAPERONE; HEAT SHOCK PROTEIN 70; HUNTINGTIN; NEF PROTEIN; POLYGLUTAMINE; PROTEIN DNAJ;

AMYOTROPHIC LATERAL SCLEROSIS; CAG REPEAT; CYSTIC FIBROSIS; DEGENERATIVE DISEASE; GENE MUTATION; HUMAN; HUNTINGTON CHOREA; KENNEDY DISEASE; NONHUMAN; PARKINSON DISEASE; PHYSICAL DISEASE BY ETIOLOGY AND PATHOGENESIS; PROTEIN AGGREGATION; PROTEIN AGGREGATION DISEASE; PROTEIN HOMEOSTASIS; REVIEW; SPINOCEREBELLAR DEGENERATION;

ANIMALS; CYSTIC FIBROSIS; HSP40 HEAT-SHOCK PROTEINS; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MICE; MOLECULAR CHAPERONES; NEURODEGENERATIVE DISEASES; PEPTIDES;

EID: 84874833124     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026611212220004     Document Type: Review

References (93)

1. Hartl, F. U.; Hayer-Hartl, M. Converging concepts of protein folding in vitro and in vivo. Nat. Struct. Mol. Biol. 2009, 16, 574-581.
2. Powers, E. T.; Morimoto, R. I.; Dillin, A.; Kelly, J. W.; Balch, W. E. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 2009, 78, 959-991.
3. Kettern, N.; Dreiseidler, M.; Tawo, R.; Hohfeld, J. Chaperone-assisted degradation: multiple paths to destruction. Biol. Chem. 2010, 391, 481-489.
4. Ritossa, F. A new puffing pattern induced by Temperature Shock and DNP in Drosophila. Experientia, 1962, 18, 571-573.
5. Tissieres, A.; Mitchell, H. K.; Tracy, U. M. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J. Mol. Biol. 1974, 84, 389-398.
6. Lindquist, S. The heat-shock response. Annu. Rev. Biochem. 1986, 55, 1151-1191.
7. Hageman, J.; van Waarde, M. A.; Zylicz, A.; Walerych, D.; Kamp-inga, H. H. The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities. Biochem. J. 2011, 435, 127-142.
8. Seidel, K.; Meister, M.; Dugbartey, G. J.; Zijlstra, M. P.; Vinet, J.; Brunt, E. R.; van Leeuwen, F. W.; Rub, U.; Kampinga, H. H.; den Dunnen, W. F. Cellular protein quality control and the evolution of aggregates in SCA3. Neuropathol. Appl. Neurobiol. 2011, 38, 548-558.
9. Liu, A. Y.; Lin, Z.; Choi, H. S.; Sorhage, F.; Li, B. Attenuated induction of heat shock gene expression in aging diploid fibro-blasts. J. Biol. Chem. 1989, 264, 12037-12045.
10. Fargnoli, J.; Kunisada, T.; Fornace, A. J., Jr; Schneider, E. L.; Hol-brook, N. J. Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. Proc. Natl. Acad. Sci. U. S. A. 1990, 87, 846-850.
11. Heydari, A. R.; You, S.; Takahashi, R.; Gutsmann-Conrad, A.; Sarge, K. D.; Richardson, A. Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes. Exp. Cell Res. 2000, 256, 83-93.
12. Westerheide, S. D.; Anckar, J.; Stevens, S. M., Jr; Sistonen, L.; Morimoto, R. I. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 2009, 323, 1063-1066.
13. Ambra, R.; Mocchegiani, E.; Giacconi, R.; Canali, R.; Rinna, A.; Malavolta, M.; Virgili, F. Characterization of the hsp70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation. Exp. Gerontol. 2004, 39, 1475-1484.
14. Marini, M.; Lapalombella, R.; Canaider, S.; Farina, A.; Monti, D.; De Vescovi, V.; Morellini, M.; Bellizzi, D.; Dato, S.; De Benedic-tis, G.; Passarino, G.; Moresi, R.; Tesei, S.; Franceschi, C. Heat shock response by EBV-immortalized B-lymphocytes from centenarians and control subjects: a model to study the relevance of stress response in longevity. Exp. Gerontol. 2004, 39, 83-90.
15. Gidalevitz, T.; Ben-Zvi, A.; Ho, K. H.; Brignull, H. R.; Morimoto, R. I. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 2006, 311, 1471-1474.
16. Kampinga, H. H.; Hageman, J.; Vos, M. J.; Kubota, H.; Tanguay, R. M.; Bruford, E. A.; Cheetham, M. E.; Chen, B.; Hightower, L.E. Guidelines for the nomenclature of the human heat shock pro teins. Cell Stress Chaperones 2009, 14, 105-111.
17. Hageman, J.; Kampinga, H. H. Computational analysis of the human HSPH/HSPA/DNAJ family and cloning of a human HSPH/HSPA/DNAJ expression library. Cell Stress Chaperones 2009, 14, 1-21.
18. 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.
19. Vos, M. J.; Hageman, J.; Carra, S.; Kampinga, H. H. Structural and functional diversities between members of the human HSPB, HSPH, HSPA, and DNAJ chaperone families. Biochemistry 2008, 47, 7001-7011.
20. Szabo, A.; Langer, T.; Schroder, H.; Flanagan, J.; Bukau, B.; Hartl, F. U. The ATP hydrolysis-dependent reaction cycle of the Es-cherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc. Natl.Acad. Sci. U. S. A. 1994, 91, 10345-10349.
21. McCarty, J. S.; Buchberger, A.; Reinstein, J.; Bukau, B. The role of ATP in the functional cycle of the DnaK chaperone system. J. Mol. Biol. 1995, 249, 126-137.
22. Laufen, T.; Mayer, M. P.; Beisel, C.; Klostermeier, D.; Mogk, A.; Reinstein, J.; Bukau, B. Mechanism of regulation of hsp70 chaper-ones by DnaJ cochaperones. Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 5452-5457.
23. Hartl, F. U.; Hayer-Hartl, M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 2002, 295, 1852-1858.
24. Bukau, B.; Weissman, J.; Horwich, A. Molecular chaperones and protein quality control. Cell 2006, 125, 443-451.
25. Nollen, E. A.; Brunsting, J. F.; Roelofsen, H.; Weber, L. A.; Kamp-inga, H. H. In vivo chaperone activity of heat shock protein 70 and thermotolerance. Mol. Cell. Biol. 1999, 19, 2069-2079.
26. Hageman, J.; Vos, M. J.; van Waarde, M. A.; Kampinga, H. H. Comparison of intra-organellar chaperone capacity for dealing with stress-induced protein unfolding. J. Biol. Chem. 2007, 282, 34334-34345.
27. Luders, J.; Demand, J.; Hohfeld, J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J. Biol. Chem. 2000, 275, 4613-4617.
28. Carra, S.; Seguin, S. J.; Lambert, H.; Landry, J. HspB8 chaperone activity toward poly(Q)-containing proteins depends on its association with Bag3, a stimulator of macroautophagy. J. Biol. Chem. 2008, 283, 1437-1444.
29. Carra, S.; Seguin, S. J.; Landry, J. HspB8 and Bag3: a new chaper-one complex targeting misfolded proteins to macroautophagy. Autophagy 2008, 4, 237-239.
30. Hata, M.; Okumura, K.; Seto, M.; Ohtsuka, K. Genomic cloning of a human heat shock protein 40 (Hsp40) gene (HSPF1) and its chromosomal localization to 19p13.2. Genomics 1996, 38, 446-449.
31. Cheetham, M. E.; Caplan, A. J. Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones 1998, 3, 28-36.
32. Ohtsuka, K.; Hata, M. Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. Cell Stress Chaperones 2000, 5, 98-112.
33. Ohtsuka, K.; Masuda, A.; Nakai, A.; Nagata, K. A novel 40-kDa protein induced by heat shock and other stresses in mammalian and avian cells. Biochem. Biophys. Res. Commun. 1990, 166, 642-647.
34. Minami, Y.; Hohfeld, J.; Ohtsuka, K.; Hartl, F. U. Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40. J. Biol. Chem. 1996, 271, 19617-19624.
35. Michels, A. A.; Kanon, B.; Bensaude, O.; Kampinga, H. H. Heat shock protein (Hsp) 40 mutants inhibit Hsp70 in mammalian cells. J. Biol. Chem. 1999, 274, 36757-36763.
36. Westhoff, B.; Chapple, J. P.; van der Spuy, J.; Hohfeld, J.; Cheetham, M. E. HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome. Curr. Biol. 2005, 15, 1058-1064.
37. Cummings, C. J.; Mancini, M. A.; Antalffy, B.; DeFranco, D. B.; Orr, H. T.; Zoghbi, H. Y. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein mis-folding in SCA1. Nat. Genet. 1998, 19, 148-154.
38. Fernandez-Funez, P.; Nino-Rosales, M. L.; de Gouyon, B.; She, W. C.; Luchak, J. M.; Martinez, P.; Turiegano, E.; Benito, J.; Ca-povilla, M.; Skinner, P. J.; McCall, A.; Canal, I.; Orr, H. T.; Zoghbi, H. Y.; Botas, J. Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 2000, 408, 101-106.
39. Rimoldi, M.; Servadio, A.; Zimarino, V. Analysis of heat shock transcription factor for suppression of polyglutamine toxicity. Brain Res. Bull. 2001, 56, 353-362.
40. Muchowski, P. J.; Schaffar, G.; Sittler, A.; Wanker, E. E.; Hayer-Hartl, M. K.; Hartl, F. U. Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 7841-7846.
41. Bailey, C. K.; Andriola, I. F.; Kampinga, H. H.; Merry, D. E. Molecular chaperones enhance the degradation of expanded polyglu-tamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2002, 11, 515-523.
42. Chai, Y.; Koppenhafer, S. L.; Bonini, N. M.; Paulson, H. L. Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. J. Neurosci. 1999, 19, 10338-10347.
43. Chan, H. Y.; Warrick, J. M.; Gray-Board, G. L.; Paulson, H. L.; Bonini, N. M. Mechanisms of chaperone suppression of polyglu-tamine disease: selectivity, synergy and modulation of protein solubility in Drosophila. Hum. Mol. Genet. 2000, 9, 2811-2820.
44. Jana, N. R.; Tanaka, M.; Wang, G.; Nukina, N. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaper-ones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet. 2000, 9, 2009-2018.
45. Rujano, M. A.; Kampinga, H. H.; Salomons, F. A. Modulation of polyglutamine inclusion formation by the Hsp70 chaperone machine. Exp. Cell Res. 2007, 313, 3568-3578.
46. Stenoien, D. L.; Cummings, C. J.; Adams, H. P.; Mancini, M. G.; Patel, K.; DeMartino, G. N.; Marcelli, M.; Weigel, N. L.; Mancini, M. A. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum. Mol. Genet. 1999, 8, 731-741.
47. Howarth, J. L.; Kelly, S.; Keasey, M. P.; Glover, C. P.; Lee, Y. B.; Mitrophanous, K.; Chapple, J. P.; Gallo, J. M.; Cheetham, M. E.; Uney, J. B. Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of po-lyglutamine disease. Mol. Ther. 2007, 15, 1100-1105.
48. Hageman, J.; Rujano, M. A.; van Waarde, M. A.; Kakkar, V.; Dirks, R. P.; Govorukhina, N.; Oosterveld-Hut, H. M.; Lubsen, N. H.; Kampinga, H. H. A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol. Cell 2010, 37, 355-369.
49. Kazemi-Esfarjani, P.; Benzer, S. Genetic suppression of polyglu-tamine toxicity in Drosophila. Science 2000, 287, 1837-1840.
50. Michels, A. A.; Kanon, B.; Konings, A. W.; Ohtsuka, K.; Ben-saude, O.; Kampinga, H. H. Hsp70 and Hsp40 chaperone activities in the cytoplasm and the nucleus of mammalian cells. J. Biol. Chem. 1997, 272, 33283-33289.
51. Wacker, J. L.; Zareie, M. H.; Fong, H.; Sarikaya, M.; Muchowski, P. J. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat. Struct. Mol. Biol. 2004, 11, 1215-1222.
52. Schaffar, G.; Breuer, P.; Boteva, R.; Behrends, C.; Tzvetkov, N.; Strippel, N.; Sakahira, H.; Siegers, K.; Hayer-Hartl, M.; Hartl, F. U. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol. Cell 2004, 15, 95-105.
53. Lotz, G. P.; Legleiter, J.; Aron, R.; Mitchell, E. J.; Huang, S. Y.; Ng, C.; Glabe, C.; Thompson, L. M.; Muchowski, P. J. Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oli-gomers in a classic ATP-dependent reaction cycle. J. Biol. Chem. 2010, 285, 38183-38193.
54. Fayazi, Z.; Ghosh, S.; Marion, S.; Bao, X.; Shero, M.; Kazemi-Esfarjani, P. A Drosophila ortholog of the human MRJ modulates polyglutamine toxicity and aggregation. Neurobiol. Dis. 2006, 24, 226-244.
55. Labbadia, J.; Novoselov, S. S.; Bett, J. S.; Weiss, A.; Paganetti, P.; Bates, G. P.; Cheetham, M. E. Suppression of protein aggregation by chaperone modification of high molecular weight complexes. Brain 2012, 135, 1180-1196.
56. Gao, X. C.; Zhou, C. J.; Zhou, Z. R.; Zhang, Y. H.; Zheng, X. M.; Song, A. X.; Hu, H. Y. Co-chaperone HSJ1a dually regulates the proteasomal degradation of ataxin-3. PLoS One 2011, 6, e19763.
57. Chuang, J. Z.; Zhou, H.; Zhu, M.; Li, S. H.; Li, X. J.; Sung, C. H. Characterization of a brain-enriched chaperone, MRJ, that inhibits Huntingtin aggregation and toxicity independently. J. Biol. Chem. 2002, 277, 19831-19838.
58. Parfitt, D. A.; Michael, G. J.; Vermeulen, E. G.; Prodromou, N. V.; Webb, T. R.; Gallo, J. M.; Cheetham, M. E.; Nicoll, W. S.; Blatch, G. L.; Chapple, J. P. The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1. Hum. Mol. Genet. 2009, 18, 1556-1565.
59. Hansson, O.; Nylandsted, J.; Castilho, R. F.; Leist, M.; Jaattela, 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.
60. Meacham, G. C.; Lu, Z.; King, S.; Sorscher, E.; Tousson, A.; Cyr, D. M. The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. EMBO J. 1999, 18, 1492-1505.
61. Abisambra, J. F.; Jinwal, U. K.; Suntharalingam, A.; Arulselvam, K.; Brady, S.; Cockman, M.; Jin, Y.; Zhang, B.; Dickey, C. A. DnaJA1 Antagonizes Constitutive Hsp70-Mediated Stabilization of Tau. J. Mol. Biol. 2012, 421, 653-661.
62. Rose, J. M.; Novoselov, S. S.; Robinson, P. A.; Cheetham, M. E. Molecular chaperone-mediated rescue of mitophagy by a Parkin RING1 domain mutant. Hum. Mol. Genet. 2011, 20, 16-27.
63. McLean, P. J.; Kawamata, H.; Shariff, S.; Hewett, J.; Sharma, N.; Ueda, K.; Breakefield, X. O.; Hyman, B. T. TorsinA and heat shock proteins act as molecular chaperones: suppression of alpha-synuclein aggregation. J. Neurochem. 2002, 83, 846-854.
64. Auluck, P. K.; Chan, H. Y.; Trojanowski, J. Q.; Lee, V. M.; Bonini, N. M. Chaperone suppression of alpha-synuclein toxicity in a Dro-sophila model for Parkinson's disease. Science 2002, 295, 865-868.
65. Berciano, M. T.; Villagra, N. T.; Ojeda, J. L.; Navascues, J.; Gomes A.; Lafarga, M.; Carmo-Fonseca, M. Oculopharyngeal muscular dystrophy-like nuclear inclusions are present in normal mag-nocellular neurosecretory neurons of the hypothalamus. Hum. Mol. Genet. 2004, 13, 829-838.
66. Takeuchi, H.; Kobayashi, Y.; Yoshihara, T.; Niwa, J.; Doyu, M.; Ohtsuka, K.; Sobue, G. Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD1. Brain Res. 2002, 949, 11-22.
67. Chien, V.; Aitken, J. F.; Zhang, S.; Buchanan, C. M.; Hickey, A.; Brittain, T.; Cooper, G. J.; Loomes, K. M. The chaperone proteins HSP70, HSP40/DnaJ and GRP78/BiP suppress misfolding and formation of beta-sheet-containing aggregates by human amylin: a potential role for defective chaperone biology in Type 2 diabetes. Biochem. J. 2010, 432, 113-121.
68. Chapple, J. P.; Cheetham, M. E. The chaperone environment at the cytoplasmic face of the endoplasmic reticulum can modulate rhodopsin processing and inclusion formation. J. Biol. Chem. 2003, 278, 19087-19094.
69. Schnaider, T.; Soti, C.; Cheetham, M. E.; Miyata, Y.; Yahara, I.; Csermely, P. Interaction of the human DnaJ homologue, HSJ1b with the 90 kDa heat shock protein, Hsp90. Life Sci. 2000, 67, 1455-1465.
70. Schmidt, B. Z.; Watts, R. J.; Aridor, M.; Frizzell, R. A. Cysteine string protein promotes proteasomal degradation of the cystic fibro-sis transmembrane conductance regulator (CFTR) by increasing its interaction with the C terminus of Hsp70-interacting protein and promoting CFTR ubiquitylation. J. Biol. Chem. 2009, 284, 4168-4178.
71. Bouchard, J. P.; Richter, A.; Mathieu, J.; Brunet, D.; Hudson, T. J.; Morgan, K.; Melancon, S. B. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Neuromuscul. Disord. 1998, 8, 474-479.
72. Engert, J. C.; Berube, P.; Mercier, J.; Dore, C.; Lepage, P.; Ge, B.; Bouchard, J. P.; Mathieu, J.; Melancon, S. B.; Schalling, M.; Lander, E. S.; Morgan, K.; Hudson, T. J.; Richter, A. ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat. Genet. 2000, 24, 120-125.
73. Vermeer, S.; Meijer, R. P.; Pijl, B. J.; Timmermans, J.; Cruysberg, J. R.; Bos, M. M.; Schelhaas, H. J.; van de Warrenburg, B. P.; Knoers, N. V.; Scheffer, H.; Kremer, B. ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia. Neu-rogenetics 2008, 9, 207-214.
74. Davey, K. M.; Parboosingh, J. S.; McLeod, D. R.; Chan, A.; Casey, R.; Ferreira, P.; Snyder, F. F.; Bridge, P. J.; Bernier, F. P. Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel auto-somal recessive Barth syndrome-like condition. J. Med. Genet. 2006, 43, 385-393.
75. Blumen, S. C.; Astord, S.; Robin, V.; Vignaud, L.; Toumi, N.; Cieslik, A.; Achiron, A.; Carasso, R. L.; Gurevich, M.; Braverman, I.; Blumen, N.; Munich, A.; Barkats, M.; Viollet, L. A rare recessive distal hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 2012, 71, 509-519.
76. Noskova, L.; Stranecky, V.; Hartmannova, H.; Pristoupilova, A.; Baresova, V.; Ivanek, R.; Hulkova, H.; Jahnova, H.; van der Zee, J.; Staropoli, J. F.; Sims, K. B.; Tyynela, J.; Van Broeckhoven, C.; Nijssen, P. C.; Mole, S. E.; Elleder, M.; Kmoch, S. Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am. J. Hum. Genet. 2011, 89, 241-252.
77. Velinov, M.; Dolzhanskaya, N.; Gonzalez, M.; Powell, E.; Koni-dari, I.; Hulme, W.; Staropoli, J. F.; Xin, W.; Wen, G. Y.; Barone, R.; Coppel, S. H.; Sims, K.; Brown, W. T.; Zuchner, S. Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families. PLoS One 2012, 7, e29729.
78. Sarparanta, J.; Jonson, P. H.; Golzio, C.; Sandell, S.; Luque, H.; Screen, M.; McDonald, K.; Stajich, J. M.; Mahjneh, I.; Vihola, A.; Raheem, O.; Penttila, S.; Lehtinen, S.; Huovinen, S.; Palmio, J.; Tasca, G.; Ricci, E.; Hackman, P.; Hauser, M.; Katsanis, N.; Udd, B. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat. Genet. 2012, 44, 450/455, S1-S2.
79. 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.
80. Bouhlal, Y.; Amouri, R.; El-Euch-Fayeche, G.; Hentati, F. Auto-somal recessive spastic ataxia of Charlevoix-Saguenay: an overview. Parkinsonism Relat. Disord. 2011, 17, 418-422.
81. Anderson, J. F.; Siller, E.; Barral, J. M. The neurodegenerative-disease-related protein sacsin is a molecular chaperone. J. Mol. Biol. 2011, 411, 870-880.
82. Girard, M.; Lariviere, R.; Parfitt, D. A.; Deane, E. C.; Gaudet, R.; Nossova, N.; Blondeau, F.; Prenosil, G.; Vermeulen, E. G.; Duchen, M. R.; Richter, A.; Shoubridge, E. A.; Gehring, K.; McKinney, R. A.; Brais, B.; Chapple, J. P.; McPherson, P. S. Mito-chondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 1661-1666.
83. Mokranjac, D.; Sichting, M.; Neupert, W.; Hell, K. Tim14, a novel key component of the import motor of the TIM23 protein translo-case of mitochondria. EMBO J. 2003, 22, 4945-4956.
84. Neupert, W.; Herrmann, J. M. Translocation of proteins into mitochondria. Annu. Rev. Biochem. 2007, 76, 723-749.
85. Evgrafov, O. V.; Mersiyanova, I.; Irobi, J.; Van Den Bosch, L.; Dierick, I.; Leung, C. L.; Schagina, O.; Verpoorten, N.; Van Impe, K.; Fedotov, V.; Dadali, E.; Auer-Grumbach, M.; Windpassinger, C.; Wagner, K.; Mitrovic, Z.; Hilton-Jones, D.; Talbot, K.; Martin, J. J.; Vasserman, N.; Tverskaya, S.; Polyakov, A.; Liem, R. K.; Gettemans, J.; Robberecht, W.; De Jonghe, P.; Timmerman, V. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nat. Genet. 2004, 36, 602-606.
86. Kolb, S. J.; Snyder, P. J.; Poi, E. J.; Renard, E. A.; Bartlett, A.; Gu, S.; Sutton, S.; Arnold, W. D.; Freimer, M. L.; Lawson, V. H.; Kissel, J.T.; Prior, T. W. Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach. Neurology 2010, 74, 502-506.
87. Irobi, J.; Van Impe, K.; Seeman, P.; Jordanova, A.; Dierick, I.; Verpoorten, N.; Michalik, A.; De Vriendt, E.; Jacobs, A.; Van Gerwen, V.; Vennekens, K.; Mazanec, R.; Tournev, I.; Hilton-Jones, D.; Talbot, K.; Kremensky, I.; Van Den Bosch, L.; Robbe-recht, W.; Van Vandekerckhove, J.; Van Broeckhoven, C.; Gette-mans, J.; De Jonghe, P.; Timmerman, V. Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. Nat. Genet. 2004, 36, 597-601.
88. Braun, J. E.; Wilbanks, S. M.; Scheller, R. H. The cysteine string secretory vesicle protein activates Hsc70 ATPase. J. Biol. Chem. 1996, 271, 25989-25993.
89. Tobaben, S.; Thakur, P.; Fernandez-Chacon, R.; Sudhof, T. C.; Rettig, J.; Stahl, B. A trimeric protein complex functions as a syn-aptic chaperone machine. Neuron 2001, 31, 987-999.
90. Burre, J.; Sharma, M.; Tsetsenis, T.; Buchman, V.; Etherton, M. R.; Sudhof, T. C. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 2010, 329, 1663-1667.
91. Sharma, M.; Burre, J.; Sudhof, T. C. CSPalpha promotes SNARE-complex assembly by chaperoning SNAP-25 during synaptic activity. Nat. Cell Biol. 2011, 13, 30-39.
92. Zhang, Y. Q.; Henderson, M. X.; Colangelo, C. M.; Ginsberg, S. D.; Bruce, C.; Wu, T.; Chandra, S. S. Identification of CSPalpha clients reveals a role in dynamin 1 regulation. Neuron 2012, 74, 136-150.
93. Johnson, J. N.; Ahrendt, E.; Braun, J. E. CSPalpha: the neuropro-tective J protein. Biochem. Cell Biol. 2010, 88, 157-165.