Department of Biology, University of Washington, Seattle, WA 98195, USA.
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Rep. 2018 Oct 23;25(4):1051-1065.e6. doi: 10.1016/j.celrep.2018.09.075.
At the cellular level, α-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, although prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila α-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but it is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in α-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation.
在细胞水平上,α-微管蛋白乙酰化改变微管的结构,使它们对压缩力具有机械抗性。微管乙酰化的这种生化特性与机械感觉的关系尚不清楚,尽管先前的研究表明微管乙酰化影响触觉感知。在这里,我们确定了主要的果蝇α-微管蛋白乙酰转移酶(dTAT),并表明它在几种机械感觉形式中发挥关键作用。dTAT 在幼虫周围神经系统(PNS)中高度表达,但对神经元形态发生基本没有影响。乙酰转移酶基因或α-微管中 K40 乙酰化位点的突变会损害感觉神经元的机械敏感性以及对轻柔触摸、强烈触摸、重力和振动刺激的行为反应,但不会损害有害热刺激的反应。最后,我们表明,dTAT 是机械诱导激活 NOMPC 所必需的,NOMPC 是一种微管相关的瞬时受体电位通道,并且在机械刺激下发挥作用以维持微管细胞骨架的完整性。