MEC-17 is an alpha-tubulin acetyltransferase.
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.
Akella
Jyothi S
JS
Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, USA.
Wloga
Dorota
D
Kim
Jihyun
J
Starostina
Natalia G
NG
Lyons-Abbott
Sally
S
Morrissette
Naomi S
NS
Dougan
Scott T
ST
Kipreos
Edward T
ET
Gaertig
Jacek
J
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002460:Cell Line; D004173:Dipodomys; D006801:Humans; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D013768:Tetrahymena / Q000378:metabolism; D014110:Touch; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015800:Protozoan Proteins; D014404:Tubulin; D029961:Zebrafish Proteins; D000123:Acetyltransferases; C552528:MEC-17 protein, C elegans; C552529:atat1 protein, zebrafish; C049182:alpha-tubulin acetylase