Skip to main content
Log in

Intracellular localization of α-tubulin acetyltransferase ATAT1 in rat ciliated cells

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Cilia are microtubule-based hair-like organelles on basal bodies located beneath the cell membrane in various tissues of multicellular animals, and are usually classified into motile cilia and primary cilia. Microtubules are assembled from the heterodimers of α- and β-tubulin. The lysine residue at position 40 (K40) of α-tubulin is an important site for acetylation, and this site is acetylated in the cilium. α-Tubulin N-acetyltransferase 1 (ATAT1) is an acetyltransferase specific to the K40 residue of α-tubulin; however, its intracellular distribution in mammalian tissues remains unclear. In this study, we analyzed ATAT1 localization in rat trachea, oviduct, kidney, retina, testis and the third ventricle of the brain by immunohistochemical techniques using a specific antibody against ATAT1. ATAT1 was distributed to the motile cilia of multiciliated cells of the trachea, third ventricle of the brain and oviduct, and in the primary cilia of the renal medullary collecting duct. ATAT1 also localized to the primary cilia, inner and outer segments of retinal photoreceptor cells, and at the Golgi apparatus of spermatocytes and spermatids of testis. These results indicated that α-tubulin acetylation by ATAT1 at distinct subcellular positions may influence the functional regulation of microtubules and cilia in a variety of ciliated cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Brown JM, Witman GB (2014) Cilia and diseases. Bioscience 64:1126–1137

    Article  PubMed  PubMed Central  Google Scholar 

  2. Satir P, Christensen ST (2007) Overview of structure and function of mammalian cilia. Annu Rev Physiol 69:377–400

    Article  CAS  PubMed  Google Scholar 

  3. Dalen H (1983) An ultrastructural study of the tracheal epithelium of the guinea-pig with special reference to the ciliary structure. J Anat 136:47–67

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Hagiwara H, Ohwada N, Aoki T, Suzuki T, Takata K (2008) The primary cilia of secretory cells in the human oviduct mucosa. Med Mol Morphol 41:193–198

    Article  PubMed  Google Scholar 

  5. Brooks Eric R, Wallingford John B (2014) Multiciliated cells. Curr Biol 24:973–982

    Article  Google Scholar 

  6. Hagiwara H, Ohwada N, Takata K (2004) Cell biology of normal and abnormal ciliogenesis in the ciliated epithelium. Int Rev Cytol 234:101–141

    Article  PubMed  Google Scholar 

  7. Pazour GJ, San Agustin JT, Follit JA, Rosenbaum JL, Witman GB (2002) Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr Biol 12:378–380

    Article  Google Scholar 

  8. Wloga D, Gaertig J (2010) Post-translational modifications of microtubules. J Cell Sci 123:3447–3455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Janke C (2014) The tubulin code: molecular components, readout mechanisms, and functions. J Cell Biol 206:461–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. LeDizet M, Piperno G (1987) Identification of an acetylation site of Chlamydomonas alpha-tubulin. Proc Natl Acad Sci U S A 84:5720–5724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Soppina V, Herbstman JF, Skiniotis G, Verhey KJ (2012) Luminal localization of α-tubulin K40 acetylation by cryo-EM analysis of fab-labeled microtubules. PLoS ONE 7:e48204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Perdiz D, Mackeh R, Poüs C, Baillet A (2011) The ins and outs of tubulin acetylation: more than just a post-translational modification? Cell Signal 23:763–771

    Article  CAS  PubMed  Google Scholar 

  13. 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 101:2085–2094

    Article  CAS  PubMed  Google Scholar 

  14. Piperno G, LeDizet M, Chang XJ (1987) Microtubules containing acetylated α-tubulin in mammalian cells in culture. J Cell Biol 104:289–302

    Article  CAS  PubMed  Google Scholar 

  15. 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 α-tubulin by the treatment with lithium chloride in human fibroblast KD cells. Med Mol Morphol 48:44–53

    Article  CAS  PubMed  Google Scholar 

  16. Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J (2010) MEC-17 is an α-tubulin acetyltransferase. Nature 467:218–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shida T, Cueva JG, Xu Z, Goodman MB, Nachury MV (2010) The major α-tubulin K40 acetyltransferase αTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci USA 107:21517–21522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Friedmann DR, Aguilar A, Fan J, Nachury MV, Marmorstein R (2012) Structure of the α-tubulin acetyltransferase, αTAT1, and implications for tubulin-specific acetylation. Proc Natl Acad Sci USA 109:19655–19660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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 287:41569–41575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Taschner M, Vetter M, Lorentzen E (2012) Atomic resolution structure of human α-tubulin acetyltransferase bound to acetyl-CoA. Proc Natl Acad Sci USA 109:19649–19654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kalebic N, Sorrentino S, Perlas E, Bolasco G, Martinez C, Heppenstall PA (2013) αTAT1 is the major α-tubulin acetyltransferase in mice. Nat Commun 4:1962

    Article  PubMed  Google Scholar 

  22. Kim G-W, Li L, Gorbani M, You L, Yang X-J (2013) Mice lacking α-tubulin acetyltransferase 1 are viable but display α-tubulin acetylation deficiency and dentate gyrus distortion. J Biol Chem 288:20334–20350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liu JP, Nakakura T, Tomura H, Tobo M, Mogi C, Wang JQ, He XD, Takano M, Damirin A, Komachi M, Sato K, Okajima F (2010) Each one of certain histidine residues in G-protein-coupled receptor GPR4 is critical for extracellular proton-induced stimulation of multiple G-protein-signaling pathways. Pharmacol Res 61:499–505

    Article  CAS  PubMed  Google Scholar 

  24. Nakakura T, Sato M, Suzuki M, Hatano O, Takemori H, Taniguchi Y, Minoshima Y, Tanaka S (2009) The spatial and temporal expression of delta-like protein 1 in the rat pituitary gland during development. Histochem Cell Biol 131:141–153

    Article  CAS  PubMed  Google Scholar 

  25. Watanabe K, Nemoto T, Akira S, Takeshita T, Shibasaki T (2013) Estrogens downregulate urocortin 2 expression in rat uterus. J Endocrinol 219:269–278

    Article  CAS  PubMed  Google Scholar 

  26. Nakakura T, Suzuki M, Watanabe Y, Tanaka S (2007) Possible involvement of brain-derived neurotrophic factor (BDNF) in the innervation of dopaminergic neurons from the rat periventricular nucleus to the pars intermedia. Zool Sci 24:1086–1093

    Article  CAS  PubMed  Google Scholar 

  27. Nakakura T, Soda A, Unno K, Suzuki M, Tanaka S (2010) Expression of IGFBP7 mRNA in corticotrophs in the anterior pituitary of adrenalectomized rats. J Histochem Cytochem 58:969–978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hagiwara H, Aoki T, Fujimoto T (1997) Ultrastructural observation on ‘transitional tubules’ in human oviductal ciliogenic cells. J Anat 191:285–290

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hagiwara H, Harada S, Maeda S, Aoki T, Ohwada N, Takata K (2002) Ultrastructural and immunohistochemical study of the basal apparatus of solitary cilia in the human oviduct epithelium. J Anat 200:89–96

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nakada T, Hagino-Yamagishi K, Nakanishi K, Yokosuka M, Saito TR, Toyoda F, Hasunuma I, Nakakura T, Kikuyama S (2014) Expression of G proteins in the olfactory receptor neurons of the newt Cynops pyrrhogaster: their unique projection into the olfactory bulbs. J Comp Neurol 522:3501–3519

    Article  CAS  PubMed  Google Scholar 

  31. Abe H, Oikawa T (1993) Observations by scanning electron microscopy of oviductal epithelial cells from cows at follicular and luteal phases. Anat Rec 235:399–410

    Article  CAS  PubMed  Google Scholar 

  32. Abe H, Hoshi H (2007) Regional and cyclic variations in the ultrastructural features of secretory cells in the oviductal epithelium of the chinese meishan pig. Reprod Domest Anim 42:292–298

    Article  CAS  PubMed  Google Scholar 

  33. Steinhauer N, Boos A, Günzel-Apel AR (2004) Morphological changes and proliferative activity in the oviductal epithelium during hormonally defined stages of the oestrous cycle in the bitch. Reprod Domest Anim 39:110–119

    Article  CAS  PubMed  Google Scholar 

  34. Latta H, Maunsbach AB, Madden SC (1961) Cilia in different segments of the rat nephron. J Biophys Biochem Cytol 11:248–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang Q, Taulman PD, Yoder BK (2004) Cystic kidney diseases: all roads lead to the cilium. Physiology 19:225–230

    Article  CAS  PubMed  Google Scholar 

  36. Sung C-H, Chuang J-Z (2010) The cell biology of vision. J Cell Biol 190:953–963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wang J, Deretic D (2014) Molecular complexes that direct rhodopsin transport to primary cilia. Prog Retin Eye Res 38:1–19

    Article  PubMed  Google Scholar 

  38. Wheway G, Parry DA, Johnson CA (2013) The role of primary cilia in the development and disease of the retina. Organogenesis 10:69–85

    Article  PubMed  PubMed Central  Google Scholar 

  39. Smith T, Spitzbarth B, Li J, Dugger D, Stern-Schneider G, Sehn E, Bolch S, McDowell JH, Tipton J, Wolfrum U, Smith WC (2013) Light-dependent phosphorylation of Bardet-Biedl syndrome 5 in photoreceptor cells modulates its interaction with arrestin1. Cell Mol Life Sci 70:4603–4616

    Article  CAS  PubMed  Google Scholar 

  40. Reidel B, Goldmann T, Giessl A, Wolfrum U (2008) The translocation of signaling molecules in dark adapting mammalian rod photoreceptor cells is dependent on the cytoskeleton. Cell Motil Cytoskeleton 65:785–800

    Article  PubMed  Google Scholar 

  41. Karam A, Tebbe L, Weber C, Messaddeq N, Morlé L, Kessler P, Wolfrum U, Trottier Y (2015) A novel function of Huntingtin in the cilium and retinal ciliopathy in Huntington’s disease mice. Neurobiol Dis 80:15–28

    Article  CAS  PubMed  Google Scholar 

  42. Parab S, Shetty O, Gaonkar R, Balasinor N, Khole V, Parte P (2015) HDAC6 deacetylates alpha tubulin in sperm and modulates sperm motility in Holtzman rat. Cell Tissue Res 359:665–678

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ms. Yuri Amakawa (Teikyo University, Itabashi, Japan) for useful technical support and Ms. Reiko Sano (Teikyo University) for technical assistance.

Funding

This work was supported in part by a Grant-in-Aid for Scientific Research (C) (24590261 to H.H) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by a research grant from Teikyo University School of Medicine.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takashi Nakakura.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest that might prejudice the impartiality of this research.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakakura, T., Suzuki, T., Nemoto, T. et al. Intracellular localization of α-tubulin acetyltransferase ATAT1 in rat ciliated cells. Med Mol Morphol 49, 133–143 (2016). https://doi.org/10.1007/s00795-015-0132-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-015-0132-1

Keywords

Navigation