Biochemistry (Moscow)

, Volume 80, Issue 13, pp 1734–1747 | Cite as

Small Heat Shock Proteins and Distal Hereditary Neuropathies

  • V. V. Nefedova
  • L. K. Muranova
  • M. V. Sudnitsyna
  • A. S. Ryzhavskaya
  • N. B. GusevEmail author


Classification of small heat shock proteins (sHsp) is presented and processes regulated by sHsp are described. Symptoms of hereditary distal neuropathy are described and the genes whose mutations are associated with development of this congenital disease are listed. The literature data and our own results concerning physicochemical properties of HspB1 mutants associated with Charcot–Marie–Tooth disease are analyzed. Mutations of HspB1, associated with hereditary motor neuron disease, can be accompanied by change of the size of HspB1 oligomers, by decreased stability under unfavorable conditions, by changes in the interaction with protein partners, and as a rule by decrease of chaperone-like activity. The largest part of these mutations is accompanied by change of oligomer stability (that can be either increased or decreased) or by change of intermonomer interaction inside an oligomer. Data on point mutation of HspB3 associated with axonal neuropathy are presented. Data concerning point mutations of Lys141 of HspB8 and those associated with hereditary neuropathy and different forms of Charcot–Marie–Tooth disease are analyzed. It is supposed that point mutations of sHsp associated with distal neuropathies lead either to loss of function (for instance, decrease of chaperone-like activity) or to gain of harmful functions (for instance, increase of interaction with certain protein partners).

Key words

small heat shock proteins phosphorylation chaperone-like activity cytoskeleton congenital diseases 



small heat shock proteins.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Maaroufi, H., and Tanguay, R. M. (2013) Analysis and phy-logeny of small heat shock proteins from marine viruses and their cyanobacteria host, PLoS One, 8, e81207.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Kriehuber, T., Rattei, T., Weinmaier, T., Bepperling, A., Haslbeck, M., and Buchner, J. (2010) Independent evolu-tion of the core domain and its flanking sequences in small heat shock proteins, FASEB J., 24, 3633–3642.PubMedCrossRefGoogle Scholar
  3. 3.
    Kappe, G., Boelens, W. C., and De Jong, W. W. (2010) Why proteins without an α-crystallin domain should not be included in the human small heat shock protein family HSPB, Cell Stress Chaperones, 15, 457–461.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Mymrikov, E. V., Seit-Nebi, A. S., and Gusev, N. B. (2011) Large potentials of small heat shock proteins, Physiol. Rev., 91, 1123–1159.PubMedCrossRefGoogle Scholar
  5. 5.
    Basha, E., O’Neill, H., and Vierling, E. (2012) Small heat shock proteins and α-crystallins: dynamic proteins with flexible functions, Trends Biochem. Sci., 37, 106–117.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Treweek, T. M., Meehan, S., Ecroyd, H., and Carver, J. A. (2014) Small heat-shock proteins: important players in regulating cellular proteostasis, Cell. Mol. Life Sci., 72, 429–451.PubMedCrossRefGoogle Scholar
  7. 7.
    Peschek, J., Braun, N., Franzmann, T. M., Georgalis, Y., Haslbeck, M., Weinkauf, S., and Buchner, J. (2009) The eye lens chaperone α-crystallin forms defined globular assemblies, Proc. Natl. Acad. Sci. USA, 106, 13272–13277.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Peschek, J., Braun, N., Rohrberg, J., Back, K. C., Kriehuber, T., Kastenmuller, A., Weinkauf, S., and Buchner, J. (2013) Regulated structural transitions unleash the chaperone activity of αB-crystallin, Proc. Natl. Acad. Sci. USA, 110, 3780–3789.CrossRefGoogle Scholar
  9. 9.
    Hochberg, G. K., and Benesch, J. L. (2014) Dynamical structure of αB-crystallin, Prog. Biophys. Mol. Biol., 115, 11–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Mymrikov, E. V., Seit-Nebi, A. S., and Gusev, N. B. (2012) Heterooligomeric complexes of human small heat shock proteins, Cell Stress Chaperones, 17, 157–169.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Arrigo, A. P. (2013) Human small heat shock proteins: pro-tein interactomes of homo-and hetero-oligomeric com-plexes: an update, FEBS Lett., 587, 1959–1969.PubMedCrossRefGoogle Scholar
  12. 12.
    Kim, K. K., Kim, R., and Kim, S. H. (1998) Crystal struc-ture of a small heat-shock protein, Nature, 394, 595–599.PubMedCrossRefGoogle Scholar
  13. 13.
    Van Montfort, R. L., Basha, E., Friedrich, K. L., Slingsby, C., and Vierling, E. (2001) Crystal structure and assembly of an eukaryotic small heat shock protein, Nat. Struct. Biol., 8, 1025–1030.PubMedCrossRefGoogle Scholar
  14. 14.
    Stamler, R., Kappe, G., Boelens, W., and Slingsby, C. (2005) Wrapping the α-crystallin domain fold in a chaper-one assembly, J. Mol. Biol., 353, 68–79.PubMedCrossRefGoogle Scholar
  15. 15.
    Hanazono, Y., Takeda, K., Yohda, M., and Miki, K. (2012) Structural studies on the oligomeric transition of a small heat shock protein, StHsp14.0, J. Mol. Biol., 422, 100–108.PubMedCrossRefGoogle Scholar
  16. 16.
    Hilario, E., Martin, F. J., Bertolini, M. C., and Fan, L. (2011) Crystal structures of Xanthomonas small heat shock protein provide a structural basis for an active molecular chaperone oligomer, J. Mol. Biol., 408, 74–86.PubMedCrossRefGoogle Scholar
  17. 17.
    Laganowsky, A., Benesch, J. L., Landau, M., Ding, L., Sawaya, M. R., Cascio, D., Huang, Q., Robinson, C. V., Horwitz, J., and Eisenberg, D. (2010) Crystal structures of truncated αA and αB crystallins reveal structural mecha-nisms of polydispersity important for eye lens function, Protein Sci., 19, 1031–1043.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Bagneris, C., Bateman, O. A., Naylor, C. E., Cronin, N., Boelens, W. C., Keep, N. H., and Slingsby, C. (2009) Crystal structures of α-crystallin domain dimers of αB-crystallin and Hsp20, J. Mol. Biol., 392, 1242–1252.PubMedCrossRefGoogle Scholar
  19. 19.
    Clark, A. R., Lubsen, N. H., and Slingsby, C. (2012) sHSP in the eye lens: crystallin mutations, cataract, and pro-teostasis, Int. J. Biochem. Cell Biol., 44, 1687–1697.PubMedCrossRefGoogle Scholar
  20. 20.
    Baranova, E. V., Weeks, S. D., Beelen, S., Bukach, O. V., Gusev, N. B., and Strelkov, S. V. (2011) Three-dimension-al structure of α-crystallin domain dimers of human small heat shock proteins HSPB1 and HSPB6, J. Mol. Biol., 411, 110–122.PubMedCrossRefGoogle Scholar
  21. 21.
    Weeks, S. D., Baranova, E. V., Heirbaut, M., Beelen, S., Shkumatov, A. V., Gusev, N. B., and Strelkov, S. V. (2014) Molecular structure and dynamics of the dimeric human small heat shock protein HSPB6, J. Struct. Biol., 185, 342–354.PubMedCrossRefGoogle Scholar
  22. 22.
    Kappe, G., Franck, E., Verschuure, P., Boelens, W. C., Leunissen, J. A., and De Jong, W. W. (2003) The human genome encodes 10 α-crystallin-related small heat shock proteins: HspB1-10, Cell Stress Chaperones, 8, 53–61.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Fontaine, J. M., Rest, J. S., Welsh, M. J., and Benndorf, R. (2003) The sperm outer dense fiber protein is the 10th member of the superfamily of mammalian small stress pro-teins, Cell Stress Chaperones, 8, 62–69.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Taylor, R. P., and Benjamin, I. J. (2005) Small heat shock proteins: a new classification scheme in mammals, J. Mol. Cell. Cardiol., 38, 433–444.PubMedCrossRefGoogle Scholar
  25. 25.
    Slingsby, C., and Wistow, G. J. (2014) Functions of crys-tallins in and out of lens: roles in elongated and post-mitot-ic cells, Prog. Biophys. Mol. Biol., 115, 52–67.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Lutsch, G., Vetter, R., Offhauss, U., Wieske, M., Grone, H. J., Klemenz, R., Schimke, I., Stahl, J., and Benndorf, R. (1997) Abundance and location of the small heat shock proteins HSP25 and αB-crystallin in rat and human heart, Circulation, 96, 3466–3476.PubMedCrossRefGoogle Scholar
  27. 27.
    Verschuure, P., Tatard, C., Boelens, W. C., Grongnet, J. F., and David, J. C. (2003) Expression of small heat shock pro-teins HspB2, HspB8, Hsp20, and cvHsp in different tissues of the perinatal developing pig, Eur. J. Cell Biol., 82, 523–530.PubMedCrossRefGoogle Scholar
  28. 28.
    Inaguma, Y., Hasegawa, K., Kato, K., and Nishida, Y. (1996) cDNA cloning of a 20-kDa protein (p20) highly homologous to small heat shock proteins: developmental and physiological changes in rat hindlimb muscles, Gene, 178, 145–150.PubMedCrossRefGoogle Scholar
  29. 29.
    Bartelt-Kirbach, B., and Golenhofen, N. (2013) Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons, Cell Stress Chaperones, 19, 145–153.PubMedCentralCrossRefGoogle Scholar
  30. 30.
    Kato, K., Shinohara, H., Goto, S., Inaguma, Y., Morishita, R., and Asano, T. (1992) Copurification of small heat shock protein with αB crystallin from human skeletal muscle, J. Biol. Chem., 267, 7718–7725.PubMedGoogle Scholar
  31. 31.
    Hilton, G. R., Lioe, H., Stengel, F., Baldwin, A. J., and Benesch, J. L. (2012) Small heat-shock proteins: para-medics of the cell, Top. Curr. Chem., 328, 69–98.CrossRefGoogle Scholar
  32. 32.
    Mymrikov, E. V., Bukach, O. V., Seit-Nebi, A. S., and Gusev, N. B. (2010) The pivotal role of the β7 strand in the intersubunit contacts of different human small heat shock proteins, Cell Stress Chaperones, 15, 365–377.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Bukach, O. V., Seit-Nebi, A. S., Marston, S. B., and Gusev, N. B. (2004) Some properties of human small heat shock protein Hsp20 (HspB6), Eur. J. Biochem., 271, 291–302.PubMedCrossRefGoogle Scholar
  34. 34.
    Carra, S., Sivilotti, M., Chavez Zobel, A. T., Lambert, H., and Landry, J. (2005) HspB8, a small heat shock protein mutated in human neuromuscular disorders, has in vivo chaperone activity in cultured cells, Hum. Mol. Genet., 14, 1659–1669.PubMedCrossRefGoogle Scholar
  35. 35.
    Boncoraglio, A., Minoia, M., and Carra, S. (2012) The family of mammalian small heat shock proteins (HSPBs): implications in protein deposit diseases and motor neu-ropathies, Int. J. Biochem. Cell Biol., 44, 1657–1669.PubMedCrossRefGoogle Scholar
  36. 36.
    Carra, S., Seguin, S. J., Lambert, H., and Landry, J. (2008) HspB8 chaperone activity toward poly(Q)-containing pro-teins depends on its association with Bag3, a stimulator of macroautophagy, J. Biol. Chem., 283, 1437–1444.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhang, H., Rajasekaran, N. S., Orosz, A., Xiao, X., Rechsteiner, M., and Benjamin, I. J. (2010) Selective degradation of aggregate-prone CryAB mutants by HSPB1 is mediated by ubiquitin-proteasome pathways, J. Mol. Cell. Cardiol., 49, 918–930.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Parcellier, A., Brunet, M., Schmitt, E., Col, E., Didelot, C., Hammann, A., Nakayama, K., Nakayama, K. I., Khochbin, S., Solary, E., and Garrido, C. (2006) HSP27 favors ubiquitination and proteasomal degradation of p27Kip1 and helps S-phase re-entry in stressed cells, FASEB J., 20, 1179–1181.PubMedCrossRefGoogle Scholar
  39. 39.
    Arrigo, A. P. (2007) The cellular “networking” of mam-malian Hsp27 and its functions in the control of protein folding, redox state, and apoptosis, Adv. Exp. Med. Biol., 594, 14–26.PubMedCrossRefGoogle Scholar
  40. 40.
    Wyttenbach, A., Sauvageot, O., Carmichael, J., Diaz-Latoud, C., Arrigo, A. P., and Rubinsztein, D. C. (2002) Heat shock protein 27 prevents cellular polyglutamine tox-icity and suppresses the increase of reactive oxygen species caused by huntingtin, Hum. Mol. Genet., 11, 1137–1151.PubMedCrossRefGoogle Scholar
  41. 41.
    Ghosh, J. G., Houck, S. A., and Clark, J. I. (2007) Interactive domains in the molecular chaperone human αB-crystallin modulate microtubule assembly and disas-sembly, PLoS One, 2, e498.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Clarke, J. P., and Mearow, K. M. (2013) Cell stress pro-motes the association of phosphorylated HspB1 with F-actin, PLoS One, 8, e68978.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Wettstein, G., Bellaye, P. S., Micheau, O., and Bonniaud, P. (2012) Small heat shock proteins and the cytoskeleton: an essential interplay for cell integrity? Int. J. Biochem. Cell Biol., 44, 1680–1686.PubMedCrossRefGoogle Scholar
  44. 44.
    Elliott, J. L., Der Perng, M., Prescott, A. R., Jansen, K. A., Koenderink, G. H., and Quinlan, R. A. (2013) The speci-ficity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability, Philos. Trans. R. Soc. Lond. B Biol. Sci., 368, doi: 10.1098/rstb.2012.0375.Google Scholar
  45. 45.
    Pivovarova, A. V., Chebotareva, N. A., Chernik, I. S., Gusev, N. B., and Levitsky, D. I. (2007) Small heat shock protein Hsp27 prevents heat-induced aggregation of F-actin by forming soluble complexes with denatured actin, FEBS J., 274, 5937–5948.PubMedCrossRefGoogle Scholar
  46. 46.
    Dreiza, C. M., Komalavilas, P., Furnish, E. J., Flynn, C. R., Sheller, M. R., Smoke, C. C., Lopes, L. B., and Brophy, C. M. (2010) The small heat shock protein, HSPB6, in muscle function and disease, Cell Stress Chaperones, 15, 1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Bakthisaran, R., Tangirala, R., and Rao, C. M. (2014) Small heat shock proteins: role in cellular functions and pathology, Biochim. Biophys. Acta, 1854, 291–319.PubMedCrossRefGoogle Scholar
  48. 48.
    Acunzo, J., Katsogiannou, M., and Rocchi, P. (2012) Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5), and HSP22 (HspB8) as regulators of cell death, Int. J. Biochem. Cell Biol., 44, 1622–1631.PubMedCrossRefGoogle Scholar
  49. 49.
    Paul, C., Simon, S., Gibert, B., Virot, S., Manero, F., and Arrigo, A. P. (2010) Dynamic processes that reflect anti-apoptotic strategies set up by HspB1 (Hsp27), Exp. Cell Res., 316, 1535–1552.PubMedCrossRefGoogle Scholar
  50. 50.
    Laskowska, E., Matuszewska, E., and Kuczynska-Wisnik, D. (2010) Small heat shock proteins and protein-misfold-ing diseases, Curr. Pharm. Biotechnol., 11, 146–157.PubMedCrossRefGoogle Scholar
  51. 51.
    Datskevich, P. N., Nefedova, V. V., Sudnitsyna, M. V., and Gusev, N. B. (2012) Mutations of small heat shock proteins and human congenital diseases, Biochemistry (Moscow), 77, 1500–1514.CrossRefGoogle Scholar
  52. 52.
    Benndorf, R., Hayess, K., Ryazantsev, S., Wieske, M., Behlke, J., and Lutsch, G. (1994) Phosphorylation and supramolecular organization of murine small heat shock protein HSP25 abolish its actin polymerization-inhibiting activity, J. Biol. Chem., 269, 20780–20784.PubMedGoogle Scholar
  53. 53.
    Bucci, C., Bakke, O., and Progida, C. (2012) Charcot–Marie–Tooth disease and intracellular traffic, Prog. Neurobiol., 99, 191–225.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Patzko, A., and Shy, M. E. (2011) Update on Charcot–Marie–Tooth disease, Curr. Neurol. Neurosci. Rep., 11, 78–88.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    DiVincenzo, C., Elzinga, C. D., Medeiros, A. C., Karbassi, I., Jones, J. R., Evans, M. C., Braastad, C. D., Bishop, C. M., Jaremko, M., Wang, Z., Liaquat, K., Hoffman, C. A., York, M. D., Batish, S. D., Lupski, J. R., and Higgins, J. J. (2014) The allelic spectrum of Charcot–Marie–Tooth dis-ease in over 17,000 individuals with neuropathy, Mol. Genet. Genom. Med., 2, 522–529.CrossRefGoogle Scholar
  56. 56.
    Gentil, B. J., and Cooper, L. (2012) Molecular basis of axonal dysfunction and traffic impairments in CMT, Brain Res. Bull., 88, 444–453.PubMedCrossRefGoogle Scholar
  57. 57.
    Timmerman, V., Strickland, A. V., and Zuchner, S. (2014) Genetics of Charcot–Marie–Tooth (CMT) disease within the frame of the human genome project success, Genes, 5, 13–32.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Jerath, N. U., and Shy, M. E. (2014) Hereditary motor and sensory neuropathies: understanding molecular pathogene-sis could lead to future treatment strategies, Biochim. Biophys. Acta, 1852, 667–678.PubMedCrossRefGoogle Scholar
  59. 59.
    Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T., Williams, M., King, C., Greenhalgh, L., Newbury-Ecob, R., and Ellard, S. (2011) Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot–Marie–Tooth disease, Am. J. Hum. Genet., 89, 308–312.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Puls, I., Jonnakuty, C., LaMonte, B. H., Holzbaur, E. L., Tokito, M., Mann, E., Floeter, M. K., Bidus, K., Drayna, D., Oh, S. J., Brown, R. H., Jr., Ludlow, C. L., and Fischbeck, K. H. (2003) Mutant dynactin in motor neuron disease, Nat. Genet., 33, 455–456.PubMedCrossRefGoogle Scholar
  61. 61.
    Zhao, C., Takita, J., Tanaka, Y., Setou, M., Nakagawa, T., Takeda, S., Yang, H. W., Terada, S., Nakata, T., Takei, Y., Saito, M., Tsuji, S., Hayashi, Y., and Hirokawa, N. (2001) Charcot–Marie–Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bβ, Cell, 105, 587–597.PubMedCrossRefGoogle Scholar
  62. 62.
    Wang, T., Ming, Z., Xiaochun, W., and Hong, W. (2011) Rab7: role of its protein interaction cascades in endo-lyso-somal traffic, Cell. Signal., 23, 516–521.PubMedCrossRefGoogle Scholar
  63. 63.
    Verhoeven, K., De Jonghe, P., Coen, K., Verpoorten, N., Auer-Grumbach, M., Kwon, J. M., FitzPatrick, D., Schmedding, E., De Vriendt, E., Jacobs, A., Van Gerwen, V., Wagner, K., Hartung, H. P., and Timmerman, V. (2003) Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot–Marie–Tooth type 2B neuropathy, Am. J. Hum. Genet., 72, 722–727.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    De Jonghe, P., Mersivanova, I., Nelis, E., Del Favero, J., Martin, J. J., Van Broeckhoven, C., Evgrafov, O., and Timmerman, V. (2001) Further evidence that neurofila-ment light chain gene mutations can cause Charcot–Marie–Tooth disease type 2E, Ann. Neurol., 49, 245–249.PubMedCrossRefGoogle Scholar
  65. 65.
    Jordanova, A., De Jonghe, P., Boerkoel, C. F., Takashima, H., De Vriendt, E., Ceuterick, C., Martin, J. J., Butler, I. J., Mancias, P., Papasozomenos, S., Terespolsky, D., Potocki, L., Brown, C. W., Shy, M., Rita, D. A., Tournev, I., Kremensky, I., Lupski, J. R., and Timmerman, V. (2003) Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot–Marie–Tooth disease, Brain, 126, 590–597.PubMedCrossRefGoogle Scholar
  66. 66.
    Mersiyanova, I. V., Perepelov, A. V., Polyakov, A. V., Sitnikov, V. F., Dadali, E. L., Oparin, R. B., Petrin, A. N., and Evgrafov, O. V. (2000) A new variant of Charcot–Marie–Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene, Am. J. Hum. Genet., 67, 37–46.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Benndorf, R., Martin, J. L., Kosakovsky Pond, S. L., and Wertheim, J. O. (2014) Neuropathy-and myopathy-associ-ated mutations in human small heat shock proteins: char-acteristics and evolutionary history of the mutation sites, Mutat. Res., doi: 10.1016/j.mrrev.2014.02.004.Google Scholar
  68. 68.
    Houlden, H., Laura, M., Wavrant de Vrieze, F., Blake, J., Wood, N., and Reilly, M. M. (2008) Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and spo-radic distal HMN/CMT type 2, Neurology, 71, 1660–1668.PubMedCrossRefGoogle Scholar
  69. 69.
    Capponi, S., Geroldi, A., Fossa, P., Grandis, M., Ciotti, P., Gulli, R., Schenone, A., Mandich, P., and Bellone, E. (2011) HSPB1 and HSPB8 in inherited neuropathies: study of an Italian cohort of dHMN and CMT2 patients, J. Peripher. Nerv. Syst., 16, 287–294.PubMedCrossRefGoogle Scholar
  70. 70.
    Muranova, L. K., Weeks, S. D., Strelkov, S. V., and Gusev, N. B. (2015) Characterization of mutants of human small heat shock protein HspB1 carrying replacements in the N-terminal domain and associated with hereditary motor neu-ron diseases, PLoS One, 10, e0126248.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    James, P. A., Rankin, J., and Talbot, K. (2008) Asymmetrical late onset motor neuropathy associated with a novel mutation in the small heat shock protein HSPB1 (HSP27), J. Neurol. Neurosurg. Psychiatry, 79, 461–463.PubMedCrossRefGoogle Scholar
  72. 72.
    Nefedova, V. V., Sudnitsyna, M. V., Strelkov, S. V., and Gusev, N. B. (2013) Structure and properties of G84R and L99M mutants of human small heat shock protein HspB1 correlating with motor neuropathy, Arch. Biochem. Biophys., 538, 16–24.PubMedCrossRefGoogle Scholar
  73. 73.
    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., and Timmerman, V. (2004) Mutant small heat-shock protein 27 causes axonal Charcot–Marie–Tooth disease and distal hereditary motor neuropathy, Nat. Genet., 36, 602–606.PubMedCrossRefGoogle Scholar
  74. 74.
    Tang, B., Liu, X., Zhao, G., Luo, W., Xia, K., Pan, Q., Cai, F., Hu, Z., Zhang, C., Chen, B., Zhang, F., Shen, L., Zhang, R., and Jiang, H. (2005) Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot–Marie–Tooth disease, Arch. Neurol., 62, 1201–1207.PubMedCrossRefGoogle Scholar
  75. 75.
    Dierick, I., Baets, J., Irobi, J., Jacobs, A., De Vriendt, E., Deconinck, T., Merlini, L., Van den Bergh, P., Rasic, V. M., Robberecht, W., Fischer, D., Morales, R. J., Mitrovic, Z., Seeman, P., Mazanec, R., Kochanski, A., Jordanova, A., Auer-Grumbach, M., Helderman van den Enden, A. T., Wokke, J. H., Nelis, E., De Jonghe, P., and Timmerman, V. (2008) Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study, Brain, 131, 1217–1227.PubMedCrossRefGoogle Scholar
  76. 76.
    Stancanelli, C., Fabrizi, G. M., Ferrarini, M., Cavallaro, T., Taioli, F., Di Leo, R., Russo, M., Gentile, L., Toscano, A., Vita, G., and Mazzeo, A. (2014) Charcot–Marie–Tooth 2F: phenotypic presentation of the Arg136Leu HSP27 mutation in a multigenerational family, Neurol. Sci., 36, 1003–1006.PubMedCrossRefGoogle Scholar
  77. 77.
    Almeida-Souza, L., Goethals, S., De Winter, V., Dierick, I., Gallardo, R., Van Durme, J., Irobi, J., Gettemans, J., Rousseau, F., Schymkowitz, J., Timmerman, V., and Janssens, S. (2010) Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot–Marie–Tooth neuropathy, J. Biol. Chem., 285, 12778–12786.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Holmgren, A., Bouhy, D., De Winter, V., Asselbergh, B., Timmermans, J. P., Irobi, J., and Timmerman, V. (2013) Charcot–Marie–Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments, Acta Neuropathol., 126, 93–108.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Srivastava, A. K., Renusch, S. R., Naiman, N. E., Gu, S., Sneh, A., Arnold, W. D., Sahenk, Z., and Kolb, S. J. (2012) Mutant HSPB1 overexpression in neurons is sufficient to cause age-related motor neuronopathy in mice, Neurobiol. Dis., 47, 163–173.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Almeida-Souza, L., Asselbergh, B., D’Ydewalle, C., Moonens, K., Goethals, S., de Winter, V., Azmi, A., Irobi, J., Timmermans, J. P., Gevaert, K., Remaut, H., Van den Bosch, L., Timmerman, V., and Janssens, S. (2011) Small heat-shock protein HSPB1 mutants stabilize microtubules in Charcot–Marie–Tooth neuropathy, J. Neurosci., 31, 15320–15328.PubMedCrossRefGoogle Scholar
  81. 81.
    D’Ydewalle, C., Krishnan, J., Chiheb, D. M., Van Damme, P., Irobi, J., Kozikowski, A. P., Van den Berghe, P., Timmerman, V., Robberecht, W., and Van den Bosch, L. (2011) HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot–Marie–Tooth disease, Nat. Med., 17, 968–974.PubMedCrossRefGoogle Scholar
  82. 82.
    Almeida-Souza, L., Timmerman, V., and Janssens, S. (2011) Microtubule dynamics in the peripheral nervous system: a matter of balance, Bioarchitecture, 1, 267–270.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Fontaine, J. M., Sun, X., Hoppe, A. D., Simon, S., Vicart, P., Welsh, M. J., and Benndorf, R. (2006) Abnormal small heat shock protein interactions involving neuropathy-associated HSP22 (HSPB8) mutants, FASEB J., 20, 2168–2170.PubMedCrossRefGoogle Scholar
  84. 84.
    Ikeda, Y., Abe, A., Ishida, C., Takahashi, K., Hayasaka, K., and Yamada, M. (2009) A clinical phenotype of distal hereditary motor neuronopathy type II with a novel HSPB1 mutation, J. Neurol. Sci., 277, 9–12.PubMedCrossRefGoogle Scholar
  85. 85.
    Nefedova, V. V., Datskevich, P. N., Sudnitsyna, M. V., Strelkov, S. V., and Gusev, N. B. (2013) Physico-chemical properties of R140G and K141Q mutants of human small heat shock protein HspB1 associated with hereditary peripheral neuropathies, Biochimie, 95, 1582–1592.PubMedCrossRefGoogle Scholar
  86. 86.
    Hansen, L., Yao, W., Eiberg, H., Kjaer, K. W., Baggesen, K., Hejtmancik, J. F., and Rosenberg, T. (2007) Genetic heterogeneity in microcornea-cataract: five novel muta-tions in CRYAA, CRYGD, and GJA8, Invest. Ophthalmol. Vis. Sci., 48, 3937–3944.PubMedCrossRefGoogle Scholar
  87. 87.
    Litt, M., Kramer, P., LaMorticella, D. M., Murphey, W., Lovrien, E. W., and Weleber, R. G. (1998) Autosomal dom-inant congenital cataract associated with a missense muta-tion in the human α-crystallin gene CRYAA, Hum. Mol. Genet., 7, 471–474.PubMedCrossRefGoogle Scholar
  88. 88.
    Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M. C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J. M., Paulin, D., and Fardeau, M. (1998) A missense muta-tion in the αB-crystallin chaperone gene causes a desmin-related myopathy, Nat. Genet., 20, 92–95.PubMedCrossRefGoogle Scholar
  89. 89.
    Inagaki, N., Hayashi, T., Arimura, T., Koga, Y., Takahashi, M., Shibata, H., Teraoka, K., Chikamori, T., Yamashina, A., and Kimura, A. (2006) αB-crystallin mutation in dilat-ed cardiomyopathy, Biochem. Biophys. Res. Commun., 342, 379–386.PubMedCrossRefGoogle Scholar
  90. 90.
    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., Robberecht, W., Van Vandekerckhove, J., Van Broeckhoven, C., Gettemans, J., De Jonghe, P., and Timmerman, V. (2004) Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy, Nat. Genet., 36, 597–601.PubMedCrossRefGoogle Scholar
  91. 91.
    Chalova, A. S., Sudnitsyna, M. V., Strelkov, S. V., and Gusev, N. B. (2014) Characterization of human small heat shock protein HspB1 that carries C-terminal domain mutations associated with hereditary motor neuron dis-eases, Biochim. Biophys. Acta, 1844, 2116–2126.PubMedCrossRefGoogle Scholar
  92. 92.
    Lin, K. P., Soong, B. W., Yang, C. C., Huang, L. W., Chang, M. H., Lee, I. H., Antonellis, A., and Lee, Y. C. (2011) The mutational spectrum in a cohort of Charcot–Marie–Tooth disease type 2 among the Han Chinese in Taiwan, PLoS One, 6, e29393.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Luigetti, M., Fabrizi, G. M., Madia, F., Ferrarini, M., Conte, A., Del Grande, A., Tasca, G., Tonali, P. A., and Sabatelli, M. (2010) A novel HSPB1 mutation in an Italian patient with CMT2/dHMN phenotype, J. Neurol. Sci., 298, 114–117.PubMedCrossRefGoogle Scholar
  94. 94.
    Kijima, K., Numakura, C., Goto, T., Takahashi, T., Otagiri, T., Umetsu, K., and Hayasaka, K. (2005) Small heat shock protein 27 mutation in a Japanese patient with distal hereditary motor neuropathy, J. Hum. Genet., 50, 473–476.PubMedCrossRefGoogle Scholar
  95. 95.
    Ackerley, S., James, P. A., Kalli, A., French, S., Davies, K. E., and Talbot, K. (2006) A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes, Hum. Mol. Genet., 15, 347–354.PubMedCrossRefGoogle Scholar
  96. 96.
    Delbecq, S. P., Jehle, S., and Klevit, R. (2012) Binding determinants of the small heat shock protein, αB-crystallin: recognition of the “IxI” motif, EMBO J., 31, 4587–4594.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Delbecq, S. P., and Klevit, R. E. (2013) One size does not fit all: the oligomeric states of αB crystallin, FEBS Lett., 587, 1073–1080.PubMedCrossRefGoogle Scholar
  98. 98.
    Hochberg, G. K., Ecroyd, H., Liu, C., Cox, D., Cascio, D., Sawaya, M. R., Collier, M. P., Stroud, J., Carver, J. A., Baldwin, A. J., Robinson, C. V., Eisenberg, D. S., Benesch, J. L., and Laganowsky, A. (2014) The structured core domain of αB-crystallin can prevent amyloid fibrilla-tion and associated toxicity, Proc. Natl. Acad. Sci. USA, 111, 1562–1570.CrossRefGoogle Scholar
  99. 99.
    Treweek, T. M., Rekas, A., Walker, M. J., and Carver, J. A. (2010) A quantitative NMR spectroscopic examination of the flexibility of the C-terminal extensions of the molecu-lar chaperones, αA-and αB-crystallin, Exp. Eye Res., 91, 691–699.PubMedCrossRefGoogle Scholar
  100. 100.
    Lindner, R. A., Carver, J. A., Ehrnsperger, M., Buchner, J., Esposito, G., Behlke, J., Lutsch, G., Kotlyarov, A., and Gaestel, M. (2000) Mouse Hsp25, a small shock protein. The role of its C-terminal extension in oligomerization and chaperone action, Eur. J. Biochem., 267, 1923–1932.PubMedCrossRefGoogle Scholar
  101. 101.
    Morris, A. M., Treweek, T. M., Aquilina, J. A., Carver, J. A., and Walker, M. J. (2008) Glutamic acid residues in the C-terminal extension of small heat shock protein 25 are critical for structural and functional integrity, FEBS J., 275, 5885–5898.PubMedCrossRefGoogle Scholar
  102. 102.
    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., and Prior, T. W. (2010) Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach, Neurology, 74, 502–506.PubMedCrossRefGoogle Scholar
  103. 103.
    Asthana, A., Raman, B., Ramakrishna, T., and Rao, C. M. (2012) Structural aspects and chaperone activity of human HspB3: role of the “C-terminal extension”, Cell Biochem. Biophys., 64, 61–72.PubMedCrossRefGoogle Scholar
  104. 104.
    Den Engelsman, J., Boros, S., Dankers, P. Y., Kamps, B., Vree Egberts, W. T., Bode, C. S., Lane, L. A., Aquilina, J. A., Benesch, J. L., Robinson, C. V., De Jong, W. W., and Boelens, W. C. (2009) The small heat-shock proteins HSPB2 and HSPB3 form well-defined heterooligomers in a unique 3 to 1 subunit ratio, J. Mol. Biol., 393, 1022–1032.PubMedCrossRefGoogle Scholar
  105. 105.
    Prabhu, S., Raman, B., Ramakrishna, T., and Rao, Ch. M. (2012) HspB2/myotonic dystrophy protein kinase binding protein (MKBP) as a novel molecular chaperone: structur-al and functional aspects, PLoS One, 7, e29810.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Hu, Z., Yang, B., Lu, W., Zhou, W., Zeng, L., Li, T., and Wang, X. (2008) HSPB2/MKBP, a novel and unique member of the small heat-shock protein family, J. Neurosci. Res., 86, 2125–2133.PubMedCrossRefGoogle Scholar
  107. 107.
    Tang, B. S., Zhao, G. H., Luo, W., Xia, K., Cai, F., Pan, Q., Zhang, R. X., Zhang, F. F., Liu, X. M., Chen, B., Zhang, C., Shen, L., Jiang, H., Long, Z. G., and Dai, H. P. (2005) Small heat-shock protein 22 mutated in autoso-mal dominant Charcot–Marie–Tooth disease type 2L, Hum. Genet., 116, 222–224.PubMedCrossRefGoogle Scholar
  108. 108.
    Nakhro, K., Park, J. M., Kim, Y. J., Yoon, B. R., Yoo, J. H., Koo, H., Choi, B. O., and Chung, K. W. (2013) A novel Lys141Thr mutation in small heat shock protein 22 (HSPB8) gene in Charcot–Marie–Tooth disease type 2L, Neuromuscul. Disord., 23, 656–663.PubMedCrossRefGoogle Scholar
  109. 109.
    Clark, A. R., Naylor, C. E., Bagneris, C., Keep, N. H., and Slingsby, C. (2011) Crystal structure of R120G disease mutant of human αB-crystallin domain dimer shows clo-sure of a groove, J. Mol. Biol., 408, 118–134.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Kasakov, A. S., Bukach, O. V., Seit-Nebi, A. S., Marston, S. B., and Gusev, N. B. (2007) Effect of mutations in the β5-β7 loop on the structure and properties of human small heat shock protein HSP22 (HspB8, H11), FEBS J., 274, 5628–5642.PubMedCrossRefGoogle Scholar
  111. 111.
    Kim, M. V., Kasakov, A. S., Seit-Nebi, A. S., Marston, S. B., and Gusev, N. B. (2006) Structure and properties of K141E mutant of small heat shock protein HSP22 (HspB8, H11) that is expressed in human neuromuscular disorders, Arch. Biochem. Biophys., 454, 32–41.PubMedCrossRefGoogle Scholar
  112. 112.
    Irobi, J., Almeida-Souza, L., Asselbergh, B., De Winter, V., Goethals, S., Dierick, I., Krishnan, J., Timmermans, J. P., Robberecht, W., De Jonghe, P., Van den Bosch, L., Janssens, S., and Timmerman, V. (2010) Mutant HSPB8 causes motor neuron-specific neurite degeneration, Hum. Mol. Genet., 19, 3254–3265.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Irobi, J., Holmgren, A., Winter, V. D., Asselbergh, B., Gettemans, J., Adriaensen, D., Groote, C. C., Coster, R. V., Jonghe, P. D., and Timmerman, V. (2012) Mutant HSPB8 causes protein aggregates and a reduced mito-chondrial membrane potential in dermal fibroblasts from distal hereditary motor neuropathy patients, Neuromuscul. Disord., doi.10.1016/j.nmd.2012.04.005.Google Scholar
  114. 114.
    Kwok, A. S., Phadwal, K., Turner, B. J., Oliver, P. L., Raw, A., Simon, A. K., Talbot, K., and Agashe, V. R. (2011) HspB8 mutation causing hereditary distal motor neuropa-thy impairs lysosomal delivery of autophagosomes, J. Neurochem., 119, 1155–1161.PubMedCrossRefGoogle Scholar
  115. 115.
    Vicario, M., Skaper, S. D., and Negro, A. (2014) The small heat shock protein HspB8: role in nervous system physiology and pathology, CNS Neurol. Disord. Drug Targets, 13, 885–895.PubMedCrossRefGoogle Scholar
  116. 116.
    Carra, S., Boncoraglio, A., Kanon, B., Brunsting, J. F., Minoia, M., Rana, A., Vos, M. J., Seidel, K., Sibon, O. C., and Kampinga, H. H. (2010) Identification of the Drosophila ortholog of HSPB8: implication of HSPB8 loss of function in protein folding diseases, J. Biol. Chem., 285, 37811–37822.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Shemetov, A. A., and Gusev, N. B. (2011) Biochemical characterization of small heat shock protein HspB8 (Hsp22)–Bag3 interaction, Arch. Biochem. Biophys., 513, 1–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Charroux, B., Pellizzoni, L., Perkinson, R. A., Shevchenko, A., Mann, M., and Dreyfuss, G. (1999) Gemin3: a novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems, J. Cell Biol., 147, 1181–1194.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Sun, X., Fontaine, J. M., Hoppe, A. D., Carra, S., De Guzman, C., Martin, J. L., Simon, S., Vicart, P., Welsh, M. J., Landry, J., and Benndorf, R. (2010) Abnormal interaction of motor neuropathy-associated mutant HspB8 (Hsp22) forms with the RNA helicase Ddx20 (gemin3), Cell Stress Chaperones, 15, 567–582.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  • V. V. Nefedova
    • 1
  • L. K. Muranova
    • 1
  • M. V. Sudnitsyna
    • 1
  • A. S. Ryzhavskaya
    • 1
  • N. B. Gusev
    • 1
    Email author
  1. 1.Faculty of BiologyLomonosov Moscow State UniversityMoscowRussia

Personalised recommendations