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Cellular and Molecular Life Sciences

, Volume 72, Issue 22, pp 4237–4255 | Cite as

Tubulin acetylation: responsible enzymes, biological functions and human diseases

  • Lin Li
  • Xiang-Jiao Yang
Review

Abstract

Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique ‘language’ to regulate microtubule structure and function.

Keywords

Tubulin code Lysine acetylation Mec17 HDAC5 SIRT2 Mechanosensing Touch receptor neuron Pillar cell Axon regeneration Inflammation HDAC inhibitor 

Notes

Acknowledgments

The research is supported by grants from Canadian Institutes of Health Research (CIHR) and Natural Sciences and Engineering Research Council of Canada (NSERC) (to X.J.Y.). L.L. received stipend support from China Scholarship Council and a Clifford C.F. Wong Scholarship.

References

  1. 1.
    Desai A, Mitchison TJ (1997) Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 13:83–117PubMedCrossRefGoogle Scholar
  2. 2.
    Nogales E (2000) Structural insights into microtubule function. Annu Rev Biochem 69:277–302PubMedCrossRefGoogle Scholar
  3. 3.
    Subramanian R, Kapoor TM (2012) Building complexity: insights into self-organized assembly of microtubule-based architectures. Dev Cell 23(5):874–885PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Westermann S, Weber K (2003) Post-translational modifications regulate microtubule function. Nat Rev Mol Cell Biol 4(12):938–947PubMedCrossRefGoogle Scholar
  5. 5.
    Wloga D, Gaertig J (2010) Post-translational modifications of microtubules. J Cell Sci 123(20):3447–3455PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Janke C, Bulinski JC (2011) Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat Rev Mol Cell Biol 12(12):773–786PubMedCrossRefGoogle Scholar
  7. 7.
    Janke C (2014) The tubulin code: molecular components, readout mechanisms, and functions. J Cell Biol 206(4):461–472PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Song Y, Brady ST (2015) Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol 25(3):125–136PubMedCrossRefGoogle Scholar
  9. 9.
    Roll-Mecak A (2015) Intrinsically disordered tubulin tails: complex tuners of microtubule functions? Semin Cell Dev Biol 37:11–19PubMedCrossRefGoogle Scholar
  10. 10.
    Barra HS, Rodrigue JA, Arce CA, Caputto R (1973) Soluble preparation from rat-brain that incorporates into its own proteins [C-14]arginine by a ribonuclease-sensitive system and [C-14]tyrosine by a ribonuclease-insensitive system. J Neurochem 20(1):97–108PubMedCrossRefGoogle Scholar
  11. 11.
    Paturle-Lafanechere L, Edde B, Denoulet P, Van Dorsselaer A, Mazarguil H, Le Caer JP, Wehland J, Job D (1991) Characterization of a major brain tubulin variant which cannot be tyrosinated. Biochemistry 30(43):10523–10528PubMedCrossRefGoogle Scholar
  12. 12.
    Lhernault SW, Rosenbaum JL (1983) Chlamydomonas alpha-tubulin is posttranslationally modified in the flagella during flagellar assembly. J Cell Biol 97(1):258–263CrossRefGoogle Scholar
  13. 13.
    Lhernault SW, Rosenbaum JL (1985) Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24(2):473–478CrossRefGoogle Scholar
  14. 14.
    Eipper BA (1974) Properties of rat-brain tubulin. J Biol Chem 249(5):1407–1416PubMedGoogle Scholar
  15. 15.
    Edde B, Rossier J, Lecaer JP, Desbruyeres E, Gros F, Denoulet P (1990) Posttranslational glutamylation of alpha-tubulin. Science 247(4938):83–85PubMedCrossRefGoogle Scholar
  16. 16.
    Redeker V, Levilliers N, Schmitter JM, Lecaer JP, Rossier J, Adoutte A, Bre MH (1994) Polyglycylation of tubulin—a posttranslational modification in axonemal microtubules. Science 266(5191):1688–1691PubMedCrossRefGoogle Scholar
  17. 17.
    Chu CW, Hou FJ, Zhang JM, Phu L, Loktev AV, Kirkpatrick DS, Jackson PK, Zhao YM, Zou H (2011) A novel acetylation of beta-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation. Mol Biol Cell 22(4):448–456PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Song Y, Kirkpatrick LL, Schilling AB, Helseth DL, Chabot N, Keillor JW, Johnson GV, Brady ST (2013) Transglutaminase and polyamination of tubulin: posttranslational modification for stabilizing axonal microtubules. Neuron 78(1):109–123PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Piroli GG, Manuel AM, Walla MD, Jepson MJ, Brock JW, Rajesh MP, Tanis RM, Cotham WE, Frizzell N (2014) Identification of protein succination as a novel modification of tubulin. Biochem J 462(2):231–245PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Alushin GM, Lander GC, Kellogg EH, Zhang R, Baker D, Nogales E (2014) High-resolution microtubule structures reveal the structural transitions in alphabeta-tubulin upon GTP hydrolysis. Cell 157(5):1117–1129PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Aiken J, Sept D, Costanzo M, Boone C, Cooper JA, Moore JK (2014) Genome-wide analysis reveals novel and discrete functions for tubulin carboxy-terminal tails. Curr Biol 24(12):1295–1303PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Sirajuddin M, Rice LM, Vale RD (2014) Regulation of microtubule motors by tubulin isotypes and post-translational modifications. Nat Cell Biol 16(4):335–344PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Erck C, Peris L, Andrieux A, Meissirel C, Gruber AD, Vernet M, Schweitzer A, Saoudi Y, Pointu H, Bosc C et al (2005) A vital role of tubulin-tyrosine-ligase for neuronal organization. Proc Natl Acad Sci USA 102(22):7853–7858PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Fernandez-Gonzalez A, La Spada AR, Treadaway J, Higdon JC, Harris BS, Sidman RL, Morgan JI, Zuo J (2002) Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1. Science 295(5561):1904–1906PubMedCrossRefGoogle Scholar
  25. 25.
    Rogowski K, van Dijk J, Magiera MM, Bosc C, Deloulme JC, Bosson A, Peris L, Gold ND, Lacroix B, Bosch Grau M et al (2010) A family of protein-deglutamylating enzymes associated with neurodegeneration. Cell 143(4):564–578PubMedCrossRefGoogle Scholar
  26. 26.
    Ikegami K, Sato S, Nakamura K, Ostrowski LE, Setou M (2010) Tubulin polyglutamylation is essential for airway ciliary function through the regulation of beating asymmetry. Proc Natl Acad Sci USA 107(23):10490–10495PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Bosch Grau M, Gonzalez Curto G, Rocha C, Magiera MM, Marques Sousa P, Giordano T, Spassky N, Janke C (2013) Tubulin glycylases and glutamylases have distinct functions in stabilization and motility of ependymal cilia. J Cell Biol 202(3):441–451PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Gershey EL, Vidali G, Allfrey VG (1968) Chemical studies of histone acetylation. The occurrence of epsilon-N-acetyllysine in the f2a1 histone. J Biol Chem 243(19):5018–5022PubMedGoogle Scholar
  29. 29.
    Piperno G, Fuller MT (1985) Monoclonal-antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms. J Cell Biol 101(6):2085–2094PubMedCrossRefGoogle Scholar
  30. 30.
    Kim SC, Sprung R, Chen Y, Xu YD, Ball H, Pei JM, Cheng TL, Kho Y, Xiao H, Xiao L et al (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23(4):607–618PubMedCrossRefGoogle Scholar
  31. 31.
    Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325(5942):834–840PubMedCrossRefGoogle Scholar
  32. 32.
    Kim GW, Yang XJ (2011) Comprehensive lysine acetylomes emerging from bacteria to humans. Trends Biochem Sci 36(4):211–220PubMedCrossRefGoogle Scholar
  33. 33.
    Mckeithan TW, Rosenbaum JL (1981) Multiple forms of tubulin in the cytoskeletal and flagellar microtubules of polytomella. J Cell Biol 91(2):352–360PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Mckeithan TW, Lefebvre PA, Silflow CD, Rosenbaum JL (1983) Multiple forms of tubulin in polytomella and chlamydomonas—evidence for a precursor of flagellar alpha-tubulin. J Cell Biol 96(4):1056–1063PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Ledizet M, Piperno G (1987) Identification of an acetylation site of Chlamydomonas alpha-tubulin. Proc Natl Acad Sci USA 84(16):5720–5724PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Piperno G, Ledizet M, Chang XJ (1987) Microtubules containing acetylated alpha-tubulin in mammalian-cells in culture. J Cell Biol 104(2):289–302PubMedCrossRefGoogle Scholar
  37. 37.
    Nakagawa U, Suzuki D, Ishikawa M, Sato H, Kamemura K, Imamura A (2013) Acetylation of alpha-tubulin on lys(40) Is a widespread post-translational modification in angiosperms. Biosci Biotechnol Biochem 77(7):1602–1605PubMedCrossRefGoogle Scholar
  38. 38.
    Yang XJ, Grégoire S (2005) Class II histone deacetylases: from sequence to function, regulation and clinical implication. Mol Cell Biol 25:2873–2884PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Greer K, Maruta H, L’Hernault SW, Rosenbaum JL (1985) Alpha-tubulin acetylase activity in isolated Chlamydomonas flagella. J Cell Biol 101(6):2081–2084PubMedCrossRefGoogle Scholar
  40. 40.
    Creppe C, Malinouskaya L, Volvert ML, Gillard M, Close P, Malaise O, Laguesse S, Cornez I, Rahmouni S, Ormenese S et al (2009) Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell 136(3):551–564PubMedCrossRefGoogle Scholar
  41. 41.
    Solinger JA, Paolinelli R, Kloss H, Scorza FB, Marchesi S, Sauder U, Mitsushima D, Capuani F, Sturzenbaum SR, Cassata G (2010) The Caenorhabditis elegans elongator complex regulates neuronal alpha-tubulin acetylation. Plos Genet 6(1)Google Scholar
  42. 42.
    Ohkawa N, Sugisaki S, Tokunaga E, Fujitani K, Hayasaka T, Setou M, Inokuchi K (2008) N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development. Genes Cells 13(11):1171–1183PubMedGoogle Scholar
  43. 43.
    Conacci-Sorrell M, Ngouenet C, Eisenman RN (2010) Myc-Nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation. Cell 142(3):480–493PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Zhang Y, Ma C, Delohery T, Nasipak B, Foat BC, Bounoutas A, Bussemaker HJ, Kim SK, Chalfie M (2002) Identification of genes expressed in C. elegans touch receptor neurons. Nature 418(6895):331–335PubMedCrossRefGoogle Scholar
  45. 45.
    Chalfie M (2009) Neurosensory mechanotransduction. Nat Rev Mol Cell Biol 10(1):44–52PubMedCrossRefGoogle Scholar
  46. 46.
    Steczkiewicz K, Kinch L, Grishin NV, Rychlewski L, Ginalski K (2006) Eukaryotic domain of unknown function DUF738 belongs to Gcn5-related N-acetyltransferase superfamily. Cell Cycle 5(24):2927–2930PubMedCrossRefGoogle Scholar
  47. 47.
    Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J (2010) MEC-17 is an alpha-tubulin acetyltransferase. Nature 467(7312):218–222. doi: 10.1038/nature09324 PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Shida T, Cueva JG, Xu ZJ, Goodman MB, Nachury MV (2010) The major alpha-tubulin K40 acetyltransferase alpha TAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci USA 107(50):21517–21522PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Kim GW, Li L, Gorbani M, You L, Yang XJ (2013) Mice lacking alpha-tubulin acetyltransferase 1 are viable but display alpha-tubulin acetylation deficiency and dentate gyrus distortion. J Biol Chem 288(28):20334–20350PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Kalebic N, Sorrentino S, Perlas E, Bolasco G, Martinez C, Heppenstall PA (2013) alpha TAT1 is the major alpha-tubulin acetyltransferase in mice. Nat Commun 4Google Scholar
  51. 51.
    Aguilar A, Becker L, Tedeschi T, Heller S, Iomini C, Nachury MV (2014) alpha-Tubulin K40 acetylation is required for contact inhibition of proliferation and cell-substrate adhesion. Mol Biol Cell 25(12):1854–1866PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Kormendi V, Szyk A, Piszczek G, Roll-Mecak A (2012) Crystal structures of tubulin acetyltransferase reveal a conserved catalytic core and the plasticity of the essential N terminus. J Biol Chem 287(50):41569–41575PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Taschner M, Vetter M, Lorentzen E (2012) Atomic resolution structure of human alpha-tubulin acetyltransferase bound to acetyl-CoA. Proc Natl Acad Sci USA 109(48):19649–19654PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Friedmann DR, Aguilar A, Fan J, Nachury MV, Marmorstein R (2012) Structure of the alpha-tubulin acetyltransferase, alphaTAT1, and implications for tubulin-specific acetylation. Proc Natl Acad Sci USA 109(48):19655–19660PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Davenport AM, Collins LN, Chiu H, Minor PJ, Sternberg PW, Hoelz A (2014) Structural and functional characterization of the alpha-tubulin acetyltransferase MEC-17. J Mol Biol 426(14):2605–2616PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Yuzawa S, Kamakura S, Hayase J, Sumimoto H (2015) Structural basis of cofactor-mediated stabilization and substrate recognition of the alpha-tubulin acetyltransferase alphaTAT1. Biochem J 467(1):103–113PubMedCrossRefGoogle Scholar
  57. 57.
    Odde D (1998) Diffusion inside microtubules. Eur Biophys J Biophys Lett 27(5):514–520CrossRefGoogle Scholar
  58. 58.
    Maruta H, Greer K, Rosenbaum JL (1986) The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules. J Cell Biol 103(2):571–579PubMedCrossRefGoogle Scholar
  59. 59.
    Szyk A, Deaconescu AM, Spector J, Goodman B, Valenstein ML, Ziolkowska NE, Kormendi V, Grigorieff N, Roll-Mecak A (2014) Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell 157(6):1405–1415PubMedCrossRefGoogle Scholar
  60. 60.
    Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417(6887):455–458PubMedCrossRefGoogle Scholar
  61. 61.
    Verdel A, Curtet S, Brocard MP, Rousseaux S, Lemercier C, Yoshida M, Khochbin S (2000) Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm. Curr Biol 10(12):747–749PubMedCrossRefGoogle Scholar
  62. 62.
    Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D, Osada H, Komatsu Y, Nishino N, Khochbin S et al (2002) In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J 21(24):6820–6831PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, Matthias P (2003) HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J 22(5):1168–1179PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (2003) The human Sir2 ortholog, SIRT2, is an NAD(+)-dependent tubulin deacetylase. Mol Cell 11(2):437–444PubMedCrossRefGoogle Scholar
  65. 65.
    Bobrowska A, Donmez G, Weiss A, Guarente L, Bates G (2012) SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of huntington’s disease phenotypes in vivo. Plos One 7(4)Google Scholar
  66. 66.
    Taes I, Timmers M, Hersmus N, Bento-Abreu A, Van den Bosch L, Van Damme P, Auwerx J, Robberecht W (2013) Hdac6 deletion delays disease progression in the SOD1(G93A) mouse model of ALS. Hum Mol Genet 22(9):1783–1790PubMedCrossRefGoogle Scholar
  67. 67.
    Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K et al (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 28(5):1688–1701PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Nagai T, Ikeda M, Chiba S, Kanno S, Mizuno K (2013) Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase. J Cell Sci 126(19):4369–4380PubMedCrossRefGoogle Scholar
  69. 69.
    Misawa T, Takahama M, Kozaki T, Lee H, Zou J, Saitoh T, Akira S (2013) Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol 14(5):454–460PubMedCrossRefGoogle Scholar
  70. 70.
    Cho Y, Cavalli V (2012) HDAC5 is a novel injury-regulated tubulin deacetylase controlling axon regeneration. EMBO J 31(14):3063–3078PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Bertos NR, Gilquin B, Chan GK, Yen TJ, Khochbin S, Yang XJ (2004) Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. J Biol Chem 279(46):48246–48254PubMedCrossRefGoogle Scholar
  72. 72.
    Liu YJ, Peng LR, Seto E, Huang SM, Qiu Y (2012) Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation. J Biol Chem 287(34):29168–29174PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C et al (2014) HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSalpha. Mol Cell 55(1):31–46PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Kovacs JJ, Murphy PJM, Gaillard S, Zhao XA, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18(5):601–607PubMedCrossRefGoogle Scholar
  75. 75.
    Cook C, Gendron TF, Scheffel K, Carlomagno Y, Dunmore J, DeTure M, Petrucelli L (2012) Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation. Hum Mol Genet 21(13):2936–2945PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Fusco C, Micale L, Augello B, Mandriani B, Pellico MT, De Nittis P, Calcagni A, Monti M, Cozzolino F, Pucci P et al (2014) HDAC6 mediates the acetylation of TRIM50. Cell Signal 26(2):363–369PubMedCrossRefGoogle Scholar
  77. 77.
    Zhang XH, Yuan ZG, Zhang YT, Yong S, Salas-Burgos A, Koomen J, Olashaw N, Parsons JT, Yang XJ, Dent SR et al (2007) HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell 27(2):197–213PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Boyault C, Zhang Y, Fritah S, Caron C, Gilquin B, Kwon SH, Garrido C, Yao TP, Vourc’h C, Matthias P et al (2007) HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev 21(17):2172–2181PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP (2003) The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115(6):727–738PubMedCrossRefGoogle Scholar
  80. 80.
    Palijan A, Fernandes I, Bastien Y, Tang LQ, Verway M, Kourelis M, Tavera-Mendoza LE, Li Z, Bourdeau V, Mader S et al (2009) Function of histone deacetylase 6 as a cofactor of nuclear receptor coregulator LCoR. J Biol Chem 284(44):30264–30274PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Chen SG, Owens GC, Makarenkova H, Edelman DB (2010) HDAC6 regulates mitochondrial transport in hippocampal neurons. Plos One 5(5)Google Scholar
  82. 82.
    Pandey UB, Nie ZP, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O et al (2007) HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447(7146):859–863PubMedCrossRefGoogle Scholar
  83. 83.
    Fukada M, Hanai A, Nakayama A, Suzuki T, Miyata N, Rodriguiz RM, Wetsel WC, Yao TP, Kawaguchi Y (2012) Loss of deacetylation activity of hdac6 affects emotional behavior in mice. Plos One 7(2)Google Scholar
  84. 84.
    Sadoul K, Wang J, Diagouraga B, Vitte AL, Buchou T, Rossini T, Polack B, Xi XD, Matthias P, Khochbin S (2012) HDAC6 controls the kinetics of platelet activation. Blood 120(20):4215–4218PubMedCrossRefGoogle Scholar
  85. 85.
    Wang B, Rao YH, Inoue M, Hao R, Lai CH, Chen D, McDonald SL, Choi MC, Wang Q, Shinohara ML et al (2014) Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production. Nat Commun 5:3479PubMedCentralPubMedGoogle Scholar
  86. 86.
    Ledizet M, Piperno G (1986) Cytoplasmic microtubules containing acetylated alpha-tubulin in Chlamydomonas-reinhardtii—spatial arrangement and properties. J Cell Biol 103(1):13–22PubMedCrossRefGoogle Scholar
  87. 87.
    Cambray-Deakin MA, Burgoyne RD (1987) Acetylated and detyrosinated alpha-tubulins are co-localized in stable microtubules in rat meningeal fibroblasts. Cell Motil Cytoskelet 8(3):284–291CrossRefGoogle Scholar
  88. 88.
    Webster DR, Borisy GG (1989) Microtubules are acetylated in domains that turn over slowly. J Cell Sci 92:57–65PubMedGoogle Scholar
  89. 89.
    Robson SJ, Burgoyne RD (1989) Differential localization of tyrosinated, detyrosinated, and acetylated alpha-tubulins in neurites and growth cones of dorsal-root ganglion neurons. Cell Motil Cytoskelet 12(4):273–282CrossRefGoogle Scholar
  90. 90.
    Sale WS, Besharse JC, Piperno G (1988) Distribution of acetylated alpha-tubulin in retina and in vitro-assembled microtubules. Cell Motil Cytoskelet 9(3):243–253CrossRefGoogle Scholar
  91. 91.
    Cambray-Deakin MA, Burgoyne RD (1987) Posttranslational modifications of alpha-tubulin: acetylated and detyrosinated forms in axons of rat cerebellum. J Cell Biol 104(6):1569–1574PubMedCrossRefGoogle Scholar
  92. 92.
    Wehland J, Weber K (1987) Turnover of the carboxy-terminal tyrosine of alpha-tubulin and means of reaching elevated levels of detyrosination in living cells. J Cell Sci 88:185–203PubMedGoogle Scholar
  93. 93.
    Bre MH, Kreis TE, Karsenti E (1987) Control of microtubule nucleation and stability in madin-darby canine kidney-cells—the occurrence of noncentrosomal, stable detyrosinated microtubules. J Cell Biol 105(3):1283–1296PubMedCrossRefGoogle Scholar
  94. 94.
    Khawaja S, Gundersen GG, Bulinski JC (1988) Enhanced stability of microtubules enriched in detyrosinated tubulin is not a direct function of detyrosination level. J Cell Biol 106(1):141–149PubMedCrossRefGoogle Scholar
  95. 95.
    Palazzo A, Ackerman B, Gundersen GG (2003) Cell biology—Tubulin acetylation and cell motility. Nature 421(6920):230PubMedCrossRefGoogle Scholar
  96. 96.
    Howes SC, Alushin GM, Shida T, Nachury MV, Nogales E (2014) Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure. Mol Biol Cell 25(2):257–266PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Barisic M, Silva ESR, Tripathy SK, Magiera MM, Zaytsev AV, Pereira AL, Janke C, Grishchuk EL, Maiato H (2015) Microtubule detyrosination guides chromosomes during mitosis. Science 348(6236):799–803PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Zilberman Y, Ballestrem C, Carramusa L, Mazitschek R, Khochbin S, Bershadsky A (2009) Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6. J Cell Sci 122(19):3531–3541PubMedCrossRefGoogle Scholar
  99. 99.
    Neumann B, Hilliard MA (2014) Loss of MEC-17 leads to microtubule instability and axonal degeneration. Cell Reports 6(1):93–103PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Tilney LG, Bryan J, Bush DJ, Fujiwara K, Mooseker MS, Murphy DB, Snyder DH (1973) Microtubules: evidence for 13 protofilaments. J Cell Biol 59(2 Pt 1):267–275PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Burton PR, Hinkley RE, Pierson GB (1975) Tannic acid-stained microtubules with 12, 13, and 15 protofilaments. J Cell Biol 65(1):227–233PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Saito K, Hama K (1982) Structural diversity of microtubules in the supporting cells of the sensory epithelium of guinea pig organ of Corti. J Electron Microsc (Tokyo) 31(3):278–281Google Scholar
  103. 103.
    Nagano T, Suzuki F (1975) Microtubules with 15 subunits in cockroach epidermal cells. J Cell Biol 64(1):242–245PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Chalfie M, Thomson JN (1979) Organization of neuronal microtubules in the nematode Caenorhabditis elegans. J Cell Biol 82(1):278–289PubMedCrossRefGoogle Scholar
  105. 105.
    Pierson GB, Burton PR, Himes RH (1979) Wall substructure of microtubules polymerized in vitro from tubulin of crayfish nerve cord and fixed with tannic acid. J Cell Sci 39:89–99PubMedGoogle Scholar
  106. 106.
    Aamodt EJ, Culotti JG (1986) Microtubules and microtubule-associated proteins from the nematode Caenorhabditis elegans: periodic cross-links connect microtubules in vitro. J Cell Biol 103(1):23–31PubMedCrossRefGoogle Scholar
  107. 107.
    Andreu JM, Bordas J, Diaz JF, Garcia de Ancos J, Gil R, Medrano FJ, Nogales E, Pantos E, Towns-Andrews E (1992) Low resolution structure of microtubules in solution. synchrotron X-ray scattering and electron microscopy of taxol-induced microtubules assembled from purified tubulin in comparison with glycerol and MAP-induced microtubules. J Mol Biol 226(1):169–184PubMedCrossRefGoogle Scholar
  108. 108.
    Moores CA, Perderiset M, Francis F, Chelly J, Houdusse A, Milligan RA (2004) Mechanism of microtubule stabilization by doublecortin. Mol Cell 14(6):833–839PubMedCrossRefGoogle Scholar
  109. 109.
    Bechstedt S, Brouhard GJ (2012) Doublecortin recognizes the 13-protofilament microtubule cooperatively and tracks microtubule ends. Dev Cell 23(1):181–192PubMedCentralPubMedCrossRefGoogle Scholar
  110. 110.
    White JG, Southgate E, Thomson JN, Brenner S (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314(1165):1–340PubMedCrossRefGoogle Scholar
  111. 111.
    Cueva JG, Mulholland A, Goodman MB (2007) Nanoscale organization of the MEC-4 DEG/ENaC sensory mechanotransduction channel in Caenorhabditis elegans touch receptor neurons. J Neurosci 27(51):14089–14098PubMedCrossRefGoogle Scholar
  112. 112.
    Topalidou I, Keller C, Kalebic N, Nguyen KCQ, Somhegyi H, Politi KA, Heppenstall P, Hall DH, Chalfie M (2012) Genetically separable functions of the MEC-17 tubulin acetyltransferase affect microtubule organization. Curr Biol 22(12):1057–1065PubMedCentralPubMedCrossRefGoogle Scholar
  113. 113.
    Siddiqui SS, Aamodt E, Rastinejad F, Culotti J (1989) Anti-tubulin monoclonal antibodies that bind to specific neurons in Caenorhabditis elegans. J Neurosci 9(8):2963–2972PubMedGoogle Scholar
  114. 114.
    Fukushige T, Siddiqui ZK, Chou M, Culotti JG, Gogonea CB, Siddiqui SS, Hamelin M (1999) MEC-12, an alpha-tubulin required for touch sensitivity in C. elegans. J Cell Sci 112(Pt 3):395–403PubMedGoogle Scholar
  115. 115.
    Cueva JG, Hsin J, Huang KC, Goodman MB (2012) Posttranslational acetylation of alpha-tubulin constrains protofilament number in native microtubules. Curr Biol 22(12):1066–1074PubMedCentralPubMedCrossRefGoogle Scholar
  116. 116.
    Tolomeo JA, Holley MC (1997) Mechanics of microtubule bundles in pillar cells from the inner ear. Biophys J 73(4):2241–2247PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Tannenbaum J, Slepecky NB (1997) Localization of microtubules containing posttranslationally modified tubulin in cochlear epithelial cells during development. Cell Motil Cytoskelet 38(2):146–162CrossRefGoogle Scholar
  118. 118.
    Reed NA, Cai DW, Blasius TL, Jih GT, Meyhofer E, Gaertig J, Verhey KJ (2006) Microtubule acetylation promotes kinesin-1 binding and transport. Curr Biol 16(21):2166–2172PubMedCrossRefGoogle Scholar
  119. 119.
    Cai DW, McEwen DP, Martens JR, Meyhofer E, Verhey KJ (2009) Single molecule imaging reveals differences in microtubule track selection between kinesin motors. Plos Biol 7(10)Google Scholar
  120. 120.
    Bhuwania R, Castro-Castro A, Linder S (2014) Microtubule acetylation regulates dynamics of KIF1C-powered vesicles and contact of microtubule plus ends with podosomes. Eur J Cell Biol 93(10–12):424–437PubMedCrossRefGoogle Scholar
  121. 121.
    Dompierre JP, Godin JD, Charrin BC, Cordelieres FP, King SJ, Humbert S, Saudou F (2007) Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J Neurosci 27(13):3571–3583PubMedCrossRefGoogle Scholar
  122. 122.
    Kaul N, Soppina V, Verhey KJ (2014) Effects of alpha-tubulin K40 acetylation and detyrosination on kinesin-1 motility in a purified system. Biophys J 106(12):2636–2643PubMedCentralPubMedCrossRefGoogle Scholar
  123. 123.
    Hammond JW, Huang CF, Kaech S, Jacobson C, Banker G, Verhey KJ (2010) Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons. Mol Biol Cell 21(4):572–583PubMedCentralPubMedCrossRefGoogle Scholar
  124. 124.
    Witte H, Neukirchen D, Bradke F (2008) Microtubule stabilization specifies initial neuronal polarization. J Cell Biol 180(3):619–632PubMedCentralPubMedCrossRefGoogle Scholar
  125. 125.
    Birdsey GM, Dryden NH, Shah AV, Hannah R, Hall MD, Haskard DO, Parsons M, Mason JC, Zvelebil M, Gottgens B et al (2012) The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis. Blood 119(3):894–903PubMedCrossRefGoogle Scholar
  126. 126.
    Li L, Wei D, Wang Q, Pan J, Liu R, Zhang X, Bao L (2012) MEC-17 deficiency leads to reduced alpha-tubulin acetylation and impaired migration of cortical neurons. J Neurosci 32(37):12673–12683PubMedCrossRefGoogle Scholar
  127. 127.
    Selvadurai K, Wang P, Seimetz J, Huang RH (2014) Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism. Nat Chem Biol 10(10):810–812PubMedCentralPubMedCrossRefGoogle Scholar
  128. 128.
    Deakin NO, Turner CE (2014) Paxillin inhibits HDAC6 to regulate microtubule acetylation, Golgi structure, and polarized migration. J Cell Biol 206(3):395–413PubMedCentralPubMedCrossRefGoogle Scholar
  129. 129.
    Montagnac G, Meas-Yedid V, Irondelle M, Castro-Castro A, Franco M, Shida T, Nachury MV, Benmerah A, Olivo-Marin JC, Chavrier P (2013) alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits. Nature 502(7472):567–570PubMedCentralPubMedCrossRefGoogle Scholar
  130. 130.
    Tran ADA, Marmo TP, Salam AA, Che S, Finkelstein E, Kabarriti R, Xenias HS, Mazitschek R, Hubbert C, Kawaguchi Y et al (2007) HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. J Cell Sci 120(8):1469–1479PubMedCrossRefGoogle Scholar
  131. 131.
    Castro-Castro A, Janke C, Montagnac G, Paul-Gilloteaux P, Chavrier P (2012) ATAT1/MEC-17 acetyltransferase and HDAC6 deacetylase control a balance of acetylation of alpha-tubulin and cortactin and regulate MT1-MMP trafficking and breast tumor cell invasion. Eur J Cell Biol 91(11–12):950–960PubMedCrossRefGoogle Scholar
  132. 132.
    Wu Y, Song SW, Sun JY, Bruner JM, Fuller GN, Zhang W (2010) IIp45 inhibits cell migration through inhibition of HDAC6. J Biol Chem 285(6):3554–3560PubMedCentralPubMedCrossRefGoogle Scholar
  133. 133.
    Penela P, Lafarga V, Tapia O, Rivas V, Nogues L, Lucas E, Vila-Bedmar R, Murga C, Mayor F (2012) Roles of GRK2 in cell signaling beyond GPCR desensitization: GRK2-HDAC6 interaction modulates cell spreading and motility. Sci Signal 5(224)Google Scholar
  134. 134.
    Chang JF, Baloh RH, Milbrandt J (2009) The NIMA-family kinase Nek3 regulates microtubule acetylation in neurons. J Cell Sci 122(13):2274–2282PubMedCentralPubMedCrossRefGoogle Scholar
  135. 135.
    Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent aurora a activation induces disassembly of the primary cilium. Cell 129(7):1351–1363PubMedCentralPubMedCrossRefGoogle Scholar
  136. 136.
    Bangs FK, Schrode N, Hadjantonakis AK, Anderson KV (2015) Lineage specificity of primary cilia in the mouse embryo. Nat Cell Biol 17(2):113–122PubMedCentralPubMedCrossRefGoogle Scholar
  137. 137.
    Nakakura T, Asano-Hoshino A, Suzuki T, Arisawa K, Tanaka H, Sekino Y, Kiuchi Y, Kawai K, Hagiwara H (2015) The elongation of primary cilia via the acetylation of alpha-tubulin by the treatment with lithium chloride in human fibroblast KD cells. Med Mol Morphol 48(1):44–53. doi: 10.1007/s00795-014-0076-x PubMedCrossRefGoogle Scholar
  138. 138.
    Loktev AV, Zhang Q, Beck JS, Searby CC, Scheetz TE, Bazan JF, Slusarski DC, Sheffield VC, Jackson PK, Nachury MV (2008) A BBSome subunit links ciliogenesis, microtubule stability, and acetylation. Dev Cell 15(6):854–865PubMedCrossRefGoogle Scholar
  139. 139.
    He Q, Wang G, Wakade S, Dasgupta S, Dinkins M, Kong JN, Spassieva SD, Bieberich E (2014) Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide. Mol Biol Cell 25(11):1715–1729PubMedCentralPubMedCrossRefGoogle Scholar
  140. 140.
    Wickstrom SA, Masoumi KC, Khochbin S, Fassler R, Massoumi R (2010) CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin. EMBO J 29(1):131–144PubMedCentralPubMedCrossRefGoogle Scholar
  141. 141.
    Eguether T, Ermolaeva MA, Zhao Y, Bonnet MC, Jain A, Pasparakis M, Courtois G, Tassin AM (2014) The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells. Nat Commun 5:4585PubMedCrossRefGoogle Scholar
  142. 142.
    Yang Y, Ran J, Liu M, Li D, Li Y, Shi X, Meng D, Pan J, Ou G, Aneja R et al (2014) CYLD mediates ciliogenesis in multiple organs by deubiquitinating Cep70 and inactivating HDAC6. Cell Res 24(11):1342–1353PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Oh EC, Katsanis N (2012) Cilia in vertebrate development and disease. Development 139(3):443–448PubMedCentralPubMedCrossRefGoogle Scholar
  144. 144.
    Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11(5):331–344PubMedCentralPubMedCrossRefGoogle Scholar
  145. 145.
    de Zoeten EF, Wang L, Butler K, Beier UH, Akimova T, Sai H, Bradner JE, Mazitschek R, Kozikowski AP, Matthias P et al (2011) Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells. Mol Cell Biol 31(10):2066–2078PubMedCentralPubMedCrossRefGoogle Scholar
  146. 146.
    Hanania R, Sun HS, Xu K, Pustylnik S, Jeganathan S, Harrison RE (2012) Classically activated macrophages use stable microtubules for matrix metalloproteinase-9 (MMP-9) secretion. J Biol Chem 287(11):8468–8483PubMedCentralPubMedCrossRefGoogle Scholar
  147. 147.
    Schroder K, Tschopp J (2010) The inflammasomes. Cell 140(6):821–832PubMedCrossRefGoogle Scholar
  148. 148.
    Misawa T, Takahama M, Kozaki T, Park S, Saitoh T, Akira S (2015) Resveratrol inhibits the acetylated alpha-tubulin-mediated assembly of the NLRP3-inflammasome. Int Immunol [Epub ahead of print]Google Scholar
  149. 149.
    Kratzer E, Tian Y, Sarich N, Wu T, Meliton A, Leff A, Birukova AA (2012) Oxidative stress contributes to lung injury and barrier dysfunction via microtubule destabilization. Am J Respir Cell Mol Biol 47(5):688–697PubMedCentralPubMedCrossRefGoogle Scholar
  150. 150.
    Ishiguro K, Ando T, Maeda O, Watanabe O, Goto H (2011) Cutting edge: tubulin alpha functions as an adaptor in NFAT-importin beta interaction. J Immunol 186(5):2710–2713PubMedCrossRefGoogle Scholar
  151. 151.
    Ishiguro K, Ando T, Maeda O, Watanabe O, Goto H (2014) Suppressive action of acetate on interleukin-8 production via tubulin-α acetylation. Immunol Cell Biol 92:624–630PubMedCrossRefGoogle Scholar
  152. 152.
    Sabo Y, Walsh D, Barry DS, Tinaztepe S, de Los Santos K, Goff SP, Gundersen GG, Naghavi MH (2013) HIV-1 induces the formation of stable microtubules to enhance early infection. Cell Host Microbe 14(5):535–546PubMedCrossRefGoogle Scholar
  153. 153.
    Valenzuela-Fernandez A, Alvarez S, Gordon-Alonso M, Barrero M, Ursa A, Cabrero JR, Fernandez G, Naranjo-Suarez S, Yanez-Mo M, Serrador JM et al (2005) Histone deacetylase 6 regulates human immunodeficiency virus type 1 infection. Mol Biol Cell 16(11):5445–5454PubMedCentralPubMedCrossRefGoogle Scholar
  154. 154.
    Husain M, Harrod KS (2011) Enhanced acetylation of alpha-tubulin in influenza A virus infected epithelial cells. FEBS Lett 585(1):128–132PubMedCrossRefGoogle Scholar
  155. 155.
    Husain M, Cheung CY (2014) Histone deacetylase 6 inhibits influenza A virus release by downregulating the trafficking of viral components to the plasma membrane via its substrate, acetylated microtubules. J Virol 88(19):11229–11239PubMedCentralPubMedCrossRefGoogle Scholar
  156. 156.
    Naranatt PP, Krishnan HH, Smith MS, Chandran B (2005) Kaposi’s sarcoma-associated herpesvirus modulates microtubule dynamics via RhoA-GTP-diaphanous 2 signaling and utilizes the dynein motors to deliver its DNA to the nucleus. J Virol 79(2):1191–1206PubMedCentralPubMedCrossRefGoogle Scholar
  157. 157.
    Zhong M, Zheng K, Chen M, Xiang Y, Jin F, Ma K, Qiu X, Wang Q, Peng T, Kitazato K et al (2014) Heat-shock protein 90 promotes nuclear transport of herpes simplex virus 1 capsid protein by interacting with acetylated tubulin. PLoS One 9(6):e99425PubMedCentralPubMedCrossRefGoogle Scholar
  158. 158.
    Li W, Zhao YZ, Chou IN (1996) Nickel (Ni2+) enhancement of alpha-tubulin acetylation in cultured 3T3 cells. Toxicol Appl Pharmacol 140(2):461–470PubMedCrossRefGoogle Scholar
  159. 159.
    Mackeh R, Lorin S, Ratier A, Mejdoubi-Charef N, Baillet A, Bruneel A, Hamai A, Codogno P, Pous C, Perdiz D (2014) Reactive oxygen species, AMP-activated protein kinase, and the transcription cofactor p300 regulate alpha- Tubulin acetyltransferase-1 (alpha TAT-1/MEC-17)- dependent microtubule hyperacetylation during cell stress. J Biol Chem 289(17):11816–11828PubMedCentralPubMedCrossRefGoogle Scholar
  160. 160.
    Pandey K, Sharma SK (2011) Activity-dependent acetylation of alpha tubulin in the hippocampus. J Mol Neurosci 45(1):1–4PubMedCrossRefGoogle Scholar
  161. 161.
    Takemura R, Okabe S, Umeyama T, Kanai Y, Cowan NJ, Hirokawa N (1992) Increased microtubule stability and alpha-tubulin acetylation in cells transfected with microtubule-associated proteins Map1b, Map2 or Tau. J Cell Sci 103:953–964PubMedGoogle Scholar
  162. 162.
    Erdozain AM, Morentin B, Bedford L, King E, Tooth D, Brewer C, Wayne D, Johnson L, Gerdes HK, Wigmore P et al (2014) Alcohol-related brain damage in humans. PLoS One 9(4):e93586PubMedCentralPubMedCrossRefGoogle Scholar
  163. 163.
    Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19(4):491–505PubMedCentralPubMedCrossRefGoogle Scholar
  164. 164.
    Sudo H, Baas PW (2010) Acetylation of microtubules influences their sensitivity to severing by katanin in neurons and fibroblasts. J Neurosci 30(21):7215–7226PubMedCentralPubMedCrossRefGoogle Scholar
  165. 165.
    Casale CH, Previtali G, Barra HS (2003) Involvement of acetylated tubulin in the regulation of Na+, K+ -ATPase activity in cultured astrocytes. FEBS Lett 534(1–3):115–118PubMedCrossRefGoogle Scholar
  166. 166.
    Santander VS, Bisig CG, Purro SA, Casale CH, Arce CA, Barra HS (2006) Tubulin must be acetylated in order to form a complex with membrane Na+, K+ -ATPase and to inhibit its enzyme activity. Mol Cell Biochem 291(1–2):167–174PubMedCrossRefGoogle Scholar
  167. 167.
    Casale CH, Previtali G, Serafino JJ, Arce CA, Barra HS (2005) Regulation of acetylated tubulin/Na+, K+-ATPase interaction by l-glutamate in non-neural cells: involvement of microtubules. Biochim Biophys Acta 1721(1–3):185–192PubMedCrossRefGoogle Scholar
  168. 168.
    Casale CH, Alonso AD, Barra HS (2001) Brain plasmamembrane NA(+), K+ -ATPase is inhibited by acetylated tubulin. Mol Cell Biochem 216(1–2):85–92PubMedCrossRefGoogle Scholar
  169. 169.
    Arce CA, Casale CH, Barra HS (2008) Submembraneous microtubule cytoskeleton: regulation of ATPases by interaction with acetylated tubulin. FEBS J 275(19):4664–4674PubMedCrossRefGoogle Scholar
  170. 170.
    Yang WL, Guo XX, Thein S, Xu F, Sugii S, Baas PW, Radda GK, Han WP (2013) Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of alpha-tubulin. Biochem J 449:605–612PubMedCrossRefGoogle Scholar
  171. 171.
    Xie R, Nguyen S, McKeehan WL, Liu LY (2010) Acetylated microtubules are required for fusion of autophagosomes with lysosomes. Bmc Cell Biol 11:89. doi: 10.1186/1471-2121-11-89 PubMedCentralPubMedCrossRefGoogle Scholar
  172. 172.
    Geeraert C, Ratier A, Pfisterer SG, Perdiz D, Cantaloube I, Rouault A, Pattingre S, Proikas-Cezanne T, Codogno P, Pous C (2010) Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation. J Biol Chem 285(31):24184–24194PubMedCentralPubMedCrossRefGoogle Scholar
  173. 173.
    d’Ydewalle C, Krishnan J, Chiheb DM, Van Damme P, Irobi J, Kozikowski AP, Vanden Berghe P, Timmerman V, Robberecht W, 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(8):968–974PubMedCrossRefGoogle Scholar
  174. 174.
    Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, Fabretti F, Janecke AR, Ebermann I, Nurnberg G et al (2011) Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. J Clin Invest 121(7):2662–2667PubMedCentralPubMedCrossRefGoogle Scholar
  175. 175.
    Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP et al (2005) A common LRRK2 mutation in idiopathic Parkinson’s disease. Lancet 365(9457):415–416PubMedGoogle Scholar
  176. 176.
    Law BM, Spain VA, Leinster VH, Chia R, Beilina A, Cho HJ, Taymans JM, Urban MK, Sancho RM, Blanca Ramirez M et al (2014) A direct interaction between leucine-rich repeat kinase 2 and specific beta-tubulin isoforms regulates tubulin acetylation. J Biol Chem 289(2):895–908PubMedCentralPubMedCrossRefGoogle Scholar
  177. 177.
    Godena VK, Brookes-Hocking N, Moller A, Shaw G, Oswald M, Sancho RM, Miller CC, Whitworth AJ, De Vos KJ (2014) Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. Nat Commun 5:5245PubMedCentralPubMedCrossRefGoogle Scholar
  178. 178.
    Govindarajan N, Rao P, Burkhardt S, Sananbenesi F, Schluter OM, Bradke F, Lu J, Fischer A (2013) Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer’s disease. EMBO Mol Med 5(1):52–63PubMedCentralPubMedCrossRefGoogle Scholar
  179. 179.
    Selenica ML, Benner L, Housley SB, Manchec B, Lee DC, Nash KR, Kalin J, Bergman JA, Kozikowski A, Gordon MN et al (2014) Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition. Alzheimers Res Ther 6(1):12PubMedCentralPubMedCrossRefGoogle Scholar
  180. 180.
    Seigneurin-Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, Khochbin S (2001) Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol Cell Biol 21(23):8035–8044PubMedCentralPubMedCrossRefGoogle Scholar
  181. 181.
    Hook SS, Orian A, Cowley SM, Eisenman RN (2002) Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes. Proc Natl Acad Sci USA 99(21):13425–13430PubMedCentralPubMedCrossRefGoogle Scholar
  182. 182.
    Yu CW, Chang PT, Hsin LW, Chern JW (2013) Quinazolin-4-one derivatives as selective histone deacetylase-6 inhibitors for the treatment of Alzheimer’s disease. J Med Chem 56(17):6775–6791PubMedCrossRefGoogle Scholar
  183. 183.
    Zhang L, Liu C, Wu J, Tao JJ, Sui XL, Yao ZG, Xu YF, Huang L, Zhu H, Sheng SL et al (2014) Tubastatin A/ACY-1215 Improves Cognition in Alzheimer’s Disease Transgenic Mice. J Alzheimers Dis 41(4):1193–1205. doi: 10.3233/JAD-140066 PubMedGoogle Scholar
  184. 184.
    Saba NF, Magliocca KR, Kim S, Muller S, Chen Z, Owonikoko TK, Sarlis NJ, Eggers C, Phelan V, Grist WJ et al (2014) Acetylated tubulin (AT) as a prognostic marker in squamous cell carcinoma of the head and neck. Head Neck Pathol 8(1):66–72PubMedCentralPubMedCrossRefGoogle Scholar
  185. 185.
    Boggs AE, Vitolo MI, Whipple RA, Charpentier MS, Goloubeva OG, Ioffe OB, Tuttle KC, Slovic J, Lu Y, Mills GB et al (2015) alpha-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration. Cancer Res 75(1):203–215PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Bailey JM, Alsina J, Rasheed ZA, McAllister FM, Fu YY, Plentz R, Zhang H, Pasricha PJ, Bardeesy N, Matsui W et al (2014) DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology 146(1):245–256PubMedCentralPubMedCrossRefGoogle Scholar
  187. 187.
    Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC et al (2012) Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 119(11):2579–2589PubMedCentralPubMedCrossRefGoogle Scholar
  188. 188.
    McLendon PM, Ferguson BS, Osinska H, Bhuiyan MS, James J, McKinsey TA, Robbins J (2014) Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy. Proc Natl Acad Sci USA 111(48):E5178–E5186PubMedCentralPubMedCrossRefGoogle Scholar
  189. 189.
    Zhang D, Wu CT, Qi X, Meijering RA, Hoogstra-Berends F, Tadevosyan A, Deniz GC, Durdu S, Akar AR, Sibon OC et al (2014) Activation of histone deacetylase-6 induces contractile dysfunction through derailment of alpha-tubulin proteostasis in experimental and human atrial fibrillation. Circulation 129(3):346–358PubMedCrossRefGoogle Scholar
  190. 190.
    Lam HC, Cloonan SM, Bhashyam AR, Haspel JA, Singh A, Sathirapongsasuti JF, Cervo M, Yao H, Chung AL, Mizumura K et al (2013) Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction. J Clin Invest 123(12):5212–5230PubMedCentralPubMedCrossRefGoogle Scholar
  191. 191.
    Nam HJ, Kang JK, Kim SK, Ahn KJ, Seok H, Park SJ, Chang JS, Pothoulakis C, Lamont JT, Kim H (2010) Clostridium difficile toxin A decreases acetylation of tubulin, leading to microtubule depolymerization through activation of histone deacetylase 6, and this mediates acute inflammation. J Biol Chem 285(43):32888–32896PubMedCentralPubMedCrossRefGoogle Scholar
  192. 192.
    Rossi A, Kontarakis Z, Gerri C, Nolte H, Holper S, Kruger M, Stainier DY (2015) Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature. doi: 10.1038/nature14580 Google Scholar
  193. 193.
    Keays DA, Tian G, Poirier K, Huang GJ, Siebold C, Cleak J, Oliver PL, Fray M, Harvey RJ, Molnar Z et al (2007) Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell 128(1):45–57PubMedCentralPubMedCrossRefGoogle Scholar
  194. 194.
    Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W, Chan WM, Andrews C, Demer JL, Robertson RL et al (2010) Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 140(1):74–87PubMedCentralPubMedCrossRefGoogle Scholar
  195. 195.
    des Portes V, Pinard JM, Billuart P, Vinet MC, Koulakoff A, Carrie A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y et al (1998) A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92(1):51–61PubMedCrossRefGoogle Scholar
  196. 196.
    Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME et al (1998) Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92(1):63–72PubMedCrossRefGoogle Scholar
  197. 197.
    Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403(6765):41–45PubMedCrossRefGoogle Scholar
  198. 198.
    Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447(7143):407–412PubMedCrossRefGoogle Scholar
  199. 199.
    Yang XJ, Seto E (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31(4):449–461PubMedCentralPubMedCrossRefGoogle Scholar
  200. 200.
    Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP (2010) Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 132(31):10842–10846PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  1. 1.Rosalind and Morris Goodman Cancer Research CenterMontrealCanada
  2. 2.Department of MedicineMontrealCanada
  3. 3.Department of BiochemistryMcGill UniversityMontrealCanada
  4. 4.McGill University Health CenterMontrealCanada

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