Acetylated tubulin is essential for touch sensation in mice
Acetylated tubulin is essential for touch sensation in mice
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DOI：
10.7554/elife.20813
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发表时间：
2016-12-13
期刊：
影响因子：
7.7
通讯作者：
Heppenstall, Paul A.
中科院分区：
文献类型：
--
作者：
Morley, Shane J.;Qi, Yanmei;Heppenstall, Paul A.
在其最基本的水平上，触觉需要将机械能转化为机械敏感离子通道开放，从而产生电化学信号。我们对这一过程的理解，特别是细胞骨架如何影响它，仍然是未知的。在这里，我们表明，小鼠缺乏α-微管蛋白乙酰转移酶Atat 1的感觉神经元显示出深刻的缺陷，他们的能力，以检测机械刺激。我们发现，所有的皮肤传入亚型，包括伤害感受器强烈降低机械敏感性Atat 1删除后，因此，小鼠在很大程度上是不敏感的机械触摸和疼痛。我们确定，这种广泛的损失mechanosensitivity是依赖于乙酰转移酶活性的Atat 1，当缺席导致细胞弹性下降。通过遗传学模拟α-微管蛋白乙酰化，我们发现细胞刚性和机械敏感性都可以在Atat 1缺陷的感觉神经元中恢复。因此，我们的研究结果表明，通过影响细胞硬度，α-微管蛋白乙酰化设置触摸所需的力。
At its most fundamental level, touch sensation requires the translation of mechanical energy into mechanosensitive ion channel opening, thereby generating electro-chemical signals. Our understanding of this process, especially how the cytoskeleton influences it, remains unknown. Here we demonstrate that mice lacking the alpha-tubulin acetyltransferase Atat1 in sensory neurons display profound deficits in their ability to detect mechanical stimuli. We show that all cutaneous afferent subtypes, including nociceptors have strongly reduced mechanosensitivity upon Atat1 deletion, and that consequently, mice are largely insensitive to mechanical touch and pain. We establish that this broad loss of mechanosensitivity is dependent upon the acetyltransferase activity of Atat1, which when absent leads to a decrease in cellular elasticity. By mimicking alpha-tubulin acetylation genetically, we show both cellular rigidity and mechanosensitivity can be restored in Atat1 deficient sensory neurons. Hence, our results indicate that by influencing cellular stiffness, alpha-tubulin acetylation sets the force required for touch.