Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, USA.
Nature. 2010 Sep 9;467(7312):218-22. doi: 10.1038/nature09324.
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.
在大多数真核细胞中，微管的亚基通过翻译后修饰（PTMs）被适当地用于特定的功能。α-微管蛋白 K40 的 ε-氨基的乙酰化是在衣滴虫的鞭毛中发现的微管内腔面的一种保守的 PTM。由于α-微管乙酰转移酶的状态尚未确定，因此对微管乙酰化意义的研究受到了限制。在这里，我们发现与 Gcn5 组蛋白乙酰转移酶相关的 MEC-17 蛋白是线虫触须神经元功能所必需的，它是α-微管蛋白 K40 的特异性乙酰转移酶。在体外，MEC-17 仅乙酰化α-微管蛋白的 K40。四膜虫 MEC-17 基因的破坏类似于 K40Rα-微管蛋白突变，使微管更加不稳定。斑马鱼中 MEC-17 的耗竭产生了与神经肌肉缺陷一致的表型。在秀丽隐杆线虫中，MEC-17 和它的同源物 W06B11.1 冗余地需要乙酰化 MEC-12α-微管蛋白，并且通过 MEC-12 乙酰化和另一种可能通过乙酰化另一种蛋白的功能来部分地贡献于触须神经元的功能。总之，我们鉴定出 MEC-17 是一种能够乙酰化α-微管蛋白 K40 残基的酶，这是唯一已知发生在微管内腔表面的 PTM。
