ATAT1-enriched vesicles promote microtubule acetylation via axonal transport
ATAT1-enriched vesicles promote microtubule acetylation via axonal transport
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DOI：
10.1126/sciadv.aax2705
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发表时间：
2019-12-01
期刊：
影响因子：
13.6
通讯作者：
Nguyen, Laurent
中科院分区：
文献类型：
--
作者：
Even, Aviel;Morelli, Giovanni;Nguyen, Laurent
微管是α-微管蛋白和β-微管蛋白的聚合二聚体，是广泛的细胞活动的基础。乙酰转移酶ATAT 1对α-微管蛋白的乙酰化调节神经元中微管动力学和功能。然而，目前还不清楚这种酶如何在轴突中长距离乙酰化微管。在这里，我们表明，ATAT 1的损失损害轴突在体内神经元的运输，和无细胞运动试验证实了适当的双向囊泡运输的α-微管蛋白乙酰化的要求。此外，我们证明了AT 1的主要细胞池在神经元囊泡的胞质侧运输，这些囊泡沿着轴突移动。总之，我们的数据表明，富含ATAT 1的囊泡的轴突运输是轴突中α-微管蛋白乙酰化的主要驱动因素。
Microtubules are polymerized dimers of alpha- and beta-tubulin that underlie a broad range of cellular activities. Acetylation of alpha-tubulin by the acetyltransferase ATAT1 modulates microtubule dynamics and functions in neurons. However, it remains unclear how this enzyme acetylates microtubules over long distances in axons. Here, we show that loss of ATAT1 impairs axonal transport in neurons in vivo, and cell-free motility assays confirm a requirement of alpha-tubulin acetylation for proper bidirectional vesicular transport. Moreover, we demonstrate that the main cellular pool of ATAT1 is transported at the cytosolic side of neuronal vesicles that are moving along axons. Together, our data suggest that axonal transport of ATAT1-enriched vesicles is the predominant driver of alpha-tubulin acetylation in axons.