alpha TAT1 controls longitudinal spreading of acetylation marks from open microtubules extremities

作者：Ly Nathalie; Elkhatib Nadia; Bresteau Enzo; Pietrement Olivier; Khaled Mehdi; Magiera Maria M; Janke Carsten; Le Cam Eric; Rutenberg Andrew D^*; Montagnac Guillaume^*

来源：Scientific Reports, 2016, 6(1): 35624.

DOI：10.1038/srep35624

Acetylation of the lysine 40 of alpha-tubulin (K40) is a post-translational modification occurring in the lumen of microtubules (MTs) and is controlled by the alpha-tubulin acetyl-transferase alpha TAT1. How alpha TAT1 accesses the lumen and acetylates alpha-tubulin there has been an open question. Here, we report that acetylation starts at open ends of MTs and progressively spreads longitudinally from there. We observed acetylation marks at the open ends of in vivo MTs re-growing after a Nocodazole block, and acetylated segments growing in length with time. Bias for MTs extremities was even more pronounced when using non-dynamic MTs extracted from HeLa cells. In contrast, K40 acetylation was mostly uniform along the length of MTs reconstituted from purified tubulin in vitro. Quantitative modelling of luminal diffusion of alpha TAT1 suggested that the uniform acetylation pattern observed in vitro is consistent with defects in the MT lattice providing lateral access to the lumen. Indeed, we observed that in vitro MTs are permeable to macromolecules along their shaft while cellular MTs are not. Our results demonstrate alpha TAT1 enters the lumen from open extremities and spreads K40 acetylation marks longitudinally along cellular MTs. This mode of tip-directed microtubule acetylation may allow for selective acetylation of subsets of microtubules.

• 出版日期2016-10-18