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Cited by 183Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesCancer Treatment and Pharmacology

Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure

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Howes, Stuart C., Alushin, Gregory M., Shida, Toshinobu, Nachury, Maxence V., Nogales, Eva·2014·Molecular Biology of the Cell
DOI 10.1091/mbc.e13-07-0387PMC PMC3890346
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Abstract

Tubulin undergoes posttranslational modifications proposed to specify microtubule subpopulations for particular functions. Most of these modifications occur on the C-termini of tubulin and may directly affect the binding of microtubule-associated proteins (MAPs) or motors. Acetylation of Lys-40 on α-tubulin is unique in that it is located on the luminal surface of microtubules, away from the interaction sites of most MAPs and motors. We investigate whether acetylation alters the architecture of microtubules or the conformation of tubulin, using cryo–electron microscopy (cryo-EM). No significant changes are observed based on protofilament distributions or microtubule helical lattice parameters. Furthermore, no clear differences in tubulin structure are detected between cryo-EM reconstructions of maximally deacetylated or acetylated microtubules. Our results indicate that the effect of acetylation must be highly localized and affect interaction with proteins that bind directly to the lumen of the microtubule. We also investigate the interaction of the tubulin acetyltransferase, αTAT1, with microtubules and find that αTAT1 is able to interact with the outside of the microtubule, at least partly through the tubulin C-termini. Binding to the outside surface of the microtubule could facilitate access of αTAT1 to its luminal site of action if microtubules undergo lateral opening between protofilaments.

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References 63 · Cited by 183

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  1. Akella JS Wloga D Kim J Starostina NG Lyons-Abbott S Morrissette NS Gaertig J MEC-17 is an α-tubulin acetyltransferase Nature 2010 467 218 222 20829795 PMC2938957
  2. Andreu JM Bordas J Diaz JF García de Ancos J Gil R Medrano FJ Towns-Andrews E 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 1992 226 169 184 1352357
  3. Arnal I Wade RH How does Taxol stabilize microtubules Curr Biol 1995 5 900 908 7583148
  4. Bouchet-Marquis C Zuber B Glynn A-M Eltsov M Grabenbauer M Goldie KN Chrétien D Visualization of cell microtubules in their native state Biol Cell 2007 99 45 53 17049046
  5. Bulinski JC Richards JE Piperno G Posttranslational modifications of alpha tubulin: detyrosination and acetylation differentiate populations of interphase microtubules in cultured cells J Cell Biol 1988 106 1213 1220 3283150 PMC2115029
  6. Burton PR Luminal material in microtubules of frog olfactory axons: structure and distribution J Cell Biol 1984 99 520 528 6430914 PMC2113267
  7. Cai D McEwen DP Martens JR Meyhofer E Verhey KJ Single molecule imaging reveals differences in microtubule track selection between kinesin motors PLoS Biol 2009 7 e1000216 19823565 PMC2749942
  8. Choudhary C Kumar C Gnad F Nielsen ML Rehman M Walther TC Mann M Lysine acetylation targets protein complexes and co-regulates major cellular functions Science 2009 325 834 40 19608861
  9. Chu CW Hou F Zhang J Phu L Loktev AV Kirkpatrick DS Zou H A novel acetylation of β-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation Mol Biol Cell 2011 22 448 456 21177827 PMC3038643
  10. Creppe C Malinouskaya L Volvert M-L Gillard M Close P Malaise O Nguyen L Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin Cell 2009 136 551 564 19185337
  11. Cueva JG Hsin J Huang KC Goodman MB Posttranslational acetylation of α-tubulin constrains protofilament number in native microtubules Curr Biol 2012 22 1066 1074 22658592 PMC3670109
  12. Danilchik MV Funk WC Brown EE Larkin K Requirement for microtubules in new membrane formation during cytokinesis of Xenopus embryos Dev Biol 1998 194 47 60 9473331
  13. De Brabander MJ Van de Veire RM Aerts FE Borgers M Janssen PA The effects of methyl (5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl) carbamate, (R 17934; NSC 238159), a new synthetic antitumoral drug interfering with microtubules, on mammalian cells cultured in vitro Cancer Res 1976 36 905 916 766963
  14. Díaz JF Barasoain I Andreu JM Fast kinetics of Taxol binding to microtubules. Effects of solution variables and microtubule-associated proteins J Biol Chem 2003 278 8407 8419 12496245
  15. Di Fulvio S Azakir BA Therrien C Sinnreich M Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation PloS One 2011 6 e28563 22174839 PMC3234273
  16. Dunn S Morrison EE Liverpool TB Molina-París C Cross RA Alonso MC Peckham M Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells J Cell Sci 2008 121 1085 1095 18334549
  17. Eddé B Rossier J Le Caer JP Desbruyères E Gros F Denoulet P Posttranslational glutamylation of alpha-tubulin Science 1990 247 83 85 1967194
  18. Egelman EH The iterative helical real space reconstruction method: surmounting the problems posed by real polymers J Struct Biol 2007 157 83 94 16919474
  19. Filippakopoulos P Knapp S The bromodomain interaction module FEBS Lett 2012 586 2692 2704 22710155
  20. Friedman JR Webster BM Mastronarde DN Verhey KJ Voeltz GK ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules J Cell Biol 2010 190 363 375 20696706 PMC2922647
  21. Friedmann DR Aguilar A Fan J Nachury MV Marmorstein R Structure of the α-tubulin acetyltransferase, αTAT1, and implications for tubulin-specific acetylation Proc Natl Acad Sci USA 2012 109 19655 19660 23071314 PMC3511727
  22. Garvalov BK Zuber B Bouchet-Marquis C Kudryashev M Gruska M Beck M Cyrklaff M Luminal particles within cellular microtubules J Cell Biol 2006 174 759 765 16954350 PMC2064330
  23. Gigant B Wang C Ravelli RBG Roussi F Steinmetz MO Curmi PA Knossow M Structural basis for the regulation of tubulin by vinblastine Nature 2005 435 519 522 15917812
  24. Janke C Bulinski JC Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions Nat Rev Mol Cell Biol 2011 12 773 786 22086369
  25. Kalebic N Martinez C Perlas E Hublitz P Bilbao-Cortes D Fiedorczuk K Heppenstall PA The tubulin acetyltransferase αTAT1 destabilizes microtubules independently of its acetylation activity Mol Cell Biol 2012 33 1114 1123 23275437 PMC3592022
  26. Konishi Y Setou M Tubulin tyrosination navigates the kinesin-1 motor domain to axons Nat Neurosci 2009 12 559 567 19377471
  27. Kormendi V Szyk A Piszczek G Roll-Mecak A Crystal structures of tubulin acetyltransferase reveal a conserved catalytic core and the plasticity of the essential N terminus J Biol Chem 2012 287 41569 41575 23105108 PMC3516708
  28. Kumar P Wittmann T +TIPs: SxIPping along microtubule ends Trends Cell Biol 2012 22 418 428 22748381 PMC3408562
  29. Lander GC Stagg SM Voss NR Cheng A Fellmann D Pulokas J Carragher B Appion: an integrated, database-driven pipeline to facilitate EM image processing J Struct Biol 2009 166 95 102 19263523 PMC2775544
  30. LeDizet M Piperno G Cytoplasmic microtubules containing acetylated alpha-tubulin in Chlamydomonas reinhardtii: spatial arrangement and properties J Cell Biol 1986 103 13 22 3722261 PMC2113809
  31. LeDizet M Piperno G Identification of an acetylation site of Chlamydomonas alpha-tubulin Proc Natl Acad Sci USA 1987 84 5720 5724 2441392 PMC298934
  32. L'Hernault SW Rosenbaum JL Chlamydomonas alpha-tubulin is posttranslationally modified in the flagella during flagellar assembly J Cell Biol 1983 97 258 263 6863393 PMC2112491
  33. L'Hernault SW Rosenbaum JL Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine Biochemistry 1985 24 473 478 3919761
  34. Li H DeRosier DJ Nicholson WV Nogales E Downing KH Microtubule structure at 8 A resolution Structure 2002 10 1317 1328 12377118
  35. Li W Zhong C Li L Sun B Wang W Xu S Zhang T Wang C Bao L Ding J Molecular basis of the acetyltransferase activity of MEC-17 towards α-tubulin Cell Res 2012 22 1707 1711 23128673 PMC3515757
  36. Maruta H Greer K Rosenbaum JL The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules J Cell Biol 1986 103 571 579 3733880 PMC2113826
  37. Meurer-Grob P Kasparian J Wade RH Microtubule structure at improved resolution Biochemistry 2001 40 8000 8008 11434769
  38. Mimori-Kiyosue Y Shiina N Tsukita S The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules Curr Biol 2000 10 865 868 10899006
  39. Nogales E Medrano FJ Diakun GP Mant GR Towns-Andrews E Bordas J The effect of temperature on the structure of vinblastine-induced polymers of purified tubulin: detection of a reversible conformational change J Mol Biol 1995 254 416 430 7490760
  40. Nogales E Whittaker M Milligan RA Downing KH High-resolution model of the microtubule Cell 1999 96 79 88 9989499
  41. North BJ Marshall BL Borra MT Denu JM Verdin E The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase Mol Cell 2003 11 437 444 12620231
  42. Odde D Diffusion inside microtubules Eur Biophys J 1998 27 514 520 9760732
  43. Perez F Diamantopoulos GS Stalder R Kreis TE CLIP-170 highlights growing microtubule ends in vivo Cell 1999 96 517 527 10052454
  44. Peris L Wagenbach M Lafanechère L Brocard J Moore AT Kozielski F Job D Wordeman L Andrieux A Motor-dependent microtubule disassembly driven by tubulin tyrosination J Cell Biol 2009 185 1159 1166 19564401 PMC2712961
  45. Pettersen EF Goddard TD Huang CC Couch GS Greenblatt DM Meng EC Ferrin TE UCSF Chimera—a visualization system for exploratory research and analysis J Comput Chem 2004 25 1605 1612 15264254
  46. Piperno G Fuller MT 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 1985 101 2085 2094 2415535 PMC2114011
  47. Quinones GB Danowski BA Devaraj A Singh V Ligon LA The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized Mol Biol Cell 2011 22 1045 1057 21307336 PMC3069008
  48. Reed NA Cai D Blasius TL Jih GT Meyhofer E Gaertig J Verhey KJ Microtubule acetylation promotes kinesin-1 binding and transport Curr Biol 2006 16 2166 2172 17084703
  49. Rice S Lin AW Safer D Hart CL Naber N Carragher BO Vale RD A structural change in the kinesin motor protein that drives motility Nature 1999 402 778 784 10617199
  50. Serrador JM Cabrero JR Sancho D Mittelbrunn M Urzainqui A Sánchez-Madrid F HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization Immunity 2004 20 417 428 15084271
  51. Shida T Cueva JG Xu Z Goodman MB Nachury MV The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation Proc Natl Acad Sci USA 2010 107 21517 21522 21068373 PMC3003046
  52. Stephens RE Tubulin in sea urchin embryonic cilia: post-translational modifications during regeneration J Cell Sci 1992 101 837 45 1527182
  53. Sudo H Baas PW Acetylation of microtubules influences their sensitivity to severing by katanin in neurons and fibroblasts J Neurosci 2010 30 7215 7226 20505088 PMC2891103
  54. Sui H Downing KH Structural basis of interprotofilament interaction and lateral deformation of microtubules Structure 2010 18 1022 1031 20696402 PMC2976607
  55. Suloway C Pulokas J Fellmann D Cheng A Guerra F Quispe J Carragher B Automated molecular microscopy: the new Leginon system J Struct Biol 2005 151 41 60 15890530
  56. Tan D Asenjo AB Mennella V Sharp DJ Sosa H Kinesin-13s form rings around microtubules J Cell Biol 2006 175 25 31 17015621 PMC2064489
  57. Tang G Peng L Baldwin PR Mann DS Jiang W Rees I Ludtke SJ EMAN2: an extensible image processing suite for electron microscopy J Struct Biol 2007 157 38 46 16859925
  58. Taschner M Vetter M Lorentzen E Atomic resolution structure of human α-tubulin acetyltransferase bound to acetyl-CoA Proc Natl Acad Sci USA 2012 109 19649 19654 23071318 PMC3511736
  59. Thyberg J Moskalewski S Relationship between the Golgi complex and microtubules enriched in detyrosinated or acetylated alpha-tubulin: studies on cells recovering from nocodazole and cells in the terminal phase of cytokinesis Cell Tissue Res 1993 273 457 466 8402828
  60. Topalidou I Keller C Kalebic N Nguyen KCQ Somhegyi H Politi KA Chalfie M Genetically separable functions of the MEC-17 tubulin acetyltransferase affect microtubule organization Curr Biol 2012 22 1057 1065 22658602 PMC3382010

Authors
Howes, S. C., Alushin, G. M., Shida, T., Nachury, M. V., & Nogales, E.
Affiliations
  • University of California, Berkeley (US)
  • Howard Hughes Medical Institute (US)
  • Stanford Medicine (US)
Corresponding author
Nogales, Eva
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2014-01-15
Volume
25
Issue
2
Pages
257-266
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e13-07-0387
PMC
PMC3890346
OpenAlex
W2112742525
Cited by
183
References
63
Citations by year
2026: 8 · 2025: 9 · 2024: 12 · 2023: 11 · 2022: 15 · 2021: 11 · 2020: 15 · 2019: 17 · 2018: 18 · 2017: 18 · 2016: 29 · 2015: 8 · 2014: 12
FWCI
9.48
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • University of California, San Francisco
  • National Institute of General Medical Sciences (T32GM008295, P01GM051487, R01GM089933)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
tubulin acetylation, microtubule structure, microtubule-associated proteins, microtubule motor proteins, post-translational modification, cryo-electron microscopy
MeSH terms
Acetylation, Acetyltransferases, Animals, Escherichia coli, Microtubule-Associated Proteins, Microtubules, Models, Molecular, Protein Binding, Protein Conformation, Protein Processing, Post-Translational, Swine, Tubulin, Kinesins, Cryoelectron Microscopy

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