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Cited by 489Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesCancer Treatment and Pharmacology

MEC-17 is an α-tubulin acetyltransferase

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Akella, Jyothi S., Wloga, Dorota, Kim, Jihyun, Starostina, Natalia G., Lyons-Abbott, Sally, Morrissette, Naomi S., Dougan, Scott T., Kipreos, Edward T. +1 more·2010·Nature
DOI 10.1038/nature09324PMC PMC2938957
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Abstract

In most eukaryotic cells, subsets of microtubules are adapted for specific functions by post-translational modifications (PTMs) of tubulin subunits. Acetylation of the epsilon-amino group of K40 on alpha-tubulin is a conserved PTM on the luminal side of microtubules that was discovered in the flagella of Chlamydomonas reinhardtii. Studies on the significance of microtubule acetylation have been limited by the undefined status of the alpha-tubulin acetyltransferase. Here we show that MEC-17, a protein related to the Gcn5 histone acetyltransferases and required for the function of touch receptor neurons in Caenorhabditis elegans, acts as a K40-specific acetyltransferase for alpha-tubulin. In vitro, MEC-17 exclusively acetylates K40 of alpha-tubulin. Disruption of the Tetrahymena MEC-17 gene phenocopies the K40R alpha-tubulin mutation and makes microtubules more labile. Depletion of MEC-17 in zebrafish produces phenotypes consistent with neuromuscular defects. In C. elegans, MEC-17 and its paralogue W06B11.1 are redundantly required for acetylation of MEC-12 alpha-tubulin, and contribute to the function of touch receptor neurons partly via MEC-12 acetylation and partly via another function, possibly by acetylating another protein. In summary, we identify MEC-17 as an enzyme that acetylates the K40 residue of alpha-tubulin, the only PTM known to occur on the luminal surface of microtubules.

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  • Treatment of cells with a tubulin deacetylase HDAC6 inhibitor (tubacin) or overexpression of the tubulin acetylase αTAT1 did not inhibit the binding of GEF-H1 to microtubules.

    “Moreover, treatment of cells with a tubulin deacetylase HDAC6 inhibitor (tubacin 54 ) or overexpression of the tubulin acetylase αTAT1 55 , both of which caused acetylation of all cellular microtubules, did not inhibit the binding of GEF-H1 to microtubules (Fig. 3a,d and Extended Data Fig. 4a,d).”

    From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [55]

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Authors
Akella, J. S., Wloga, D., Kim, J., Starostina, N. G., Lyons-Abbott, S., Morrissette, N. S., Dougan, S. T., Kipreos, E. T., & Gaertig, J.
Affiliations
  • University of Georgia (US)
  • University of California, Irvine (US)
Corresponding author
Gaertig, Jacek
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2010-09
Volume
467
Issue
7312
Pages
218-222
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature09324
PMC
PMC2938957
OpenAlex
W1585324347
Cited by
489
References
1
Citations by year
2026: 18 · 2025: 37 · 2024: 22 · 2023: 22 · 2022: 28 · 2021: 34 · 2020: 37 · 2019: 28 · 2018: 29 · 2017: 24 · 2016: 38 · 2015: 29 · 2014: 43 · 2013: 35 · 2012: 37
FWCI
13.99
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Science Foundation
  • Georgia Cancer Coalition
  • University of Rochester
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM074212, R01GM089912)
  • National Institute of Allergy and Infectious Diseases (R01AI067981)
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
alpha-tubulin acetylation, microtubule acetylation, acetyltransferase, touch receptor neurons, Caenorhabditis elegans, Tetrahymena, zebrafish, mec-12, cell polarity
MeSH terms
Acetylation, Acetyltransferases, Animals, Cell Line, Dipodomys, Humans, Tetrahymena, Touch, Tubulin, Zebrafish, Protozoan Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Zebrafish Proteins

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