MEC-17 is an α-tubulin acetyltransferase

Abstract

In most eukaryotic cells, subsets of microtubules are adapted for specific functions by post-translational modifications (PTMs) of tubulin subunits. Acetylation of the ε-amino group of K40 on α-tubulin is a conserved PTM on the luminal side of microtubules1 that was discovered in the flagella of Chlamydomonas reinhardtii2,3. Studies on the significance of microtubule acetylation have been limited by the undefined status of the α-tubulin acetyltransferase. Here we show that MEC-17, a protein related to the Gcn5 histone acetyltransferases4 and required for the function of touch receptor neurons in Caenorhabditis elegans5,6, acts as a K40-specific acetyltransferase for α-tubulin. In vitro, MEC-17 exclusively acetylates K40 of α-tubulin. Disruption of the Tetrahymena MEC-17 gene phenocopies the K40R α-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 α-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 α-tubulin, the only PTM known to occur on the luminal surface of microtubules.

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Figure 1: MEC-17 is required for acetylation of K40 on α-tubulin in Tetrahymena.
Figure 2: MEC-17 and W06B11.1 are required for acetylation of K40 and contribute to touch sensation in C. elegans.
Figure 3: MEC-17 is required for K40 acetylation in zebrafish and normal embryonic development.
Figure 4: MEC-17 controls the levels of microtubule acetylation in mammalian cells.
Figure 5: MEC-17 has intrinsic, K40-specific α-TAT activity.

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Acknowledgements

This work was supported by funds from the National Science Foundation (MBC-033965 to J.G.), American Cancer Society (RSG DDC-112979 to S.T.D.), and National Institutes of Health (R01GM074212 to E.T.K., R01AI067981 to N.S.M., R01GM089912 to J.G.). S.T.D. is a Georgia Cancer Coalition Distinguished Investigator. We are grateful to M. Chalfie for the mec-12(e1607) mutant, J. Frankel for 12G10 mAb (available from the Developmental Studies Hybridoma Bank), M. Gorovsky for SG anti-tubulin antibodies, D. Allis for anti-hv1 antibodies, B. Feldman for mismatch morpholinos, and S. T. Dougan laboratory members for advice and assistance with zebrafish experiments.

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J.S.A., D.W., J.K., N.G.S., S.L.-A., S.T.D., E.T.K. and J.G. designed and performed the experiments. N.S.M., S.T.D., E.T.K. and J.G. supervised the work in their respective laboratories. J.G. integrated data and wrote drafts of the paper that were edited by all co-authors.

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Correspondence to Jacek Gaertig.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Tables 1-2, and Supplementary Figures 1-8, with legends. (PDF 3547 kb)

Supplementary Movie 1

The movie shows zebrafish embryos injected with 1 ng of random sequence morpholinos and recorded at 48 hpf. (MOV 4228 kb)

Supplementary Movie 2

The movie shows zebrafish embryos injected with 1 ng of MEC17-ATG morpholinos and recorded at 48 hpf. (MOV 7074 kb)

Supplementary Movie 3

The movie shows zebrafish embryps injected with 1 ng of MEC17-SP morpholinos and recorded at 48 hpf. (MOV 7043 kb)

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Akella, J., Wloga, D., Kim, J. et al. MEC-17 is an α-tubulin acetyltransferase. Nature 467, 218–222 (2010). https://doi.org/10.1038/nature09324

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