Acetylated tubulin is essential for touch sensation in mice

Abstract

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 α-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 α-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, α-tubulin acetylation sets the force required for touch.DOI: http://dx.doi.org/10.7554/eLife.20813.001

Microtubule Acetylation Is Required for Mechanosensation in Drosophila

“…In cultured mechanosensory dorsal root ganglion (DRG) neurons, acTb appears to be concentrated in a submembrane band (Morley et al, 2016). We therefore hypothesized that acTb would be similarly concentrated in mechanosensory c3da neurons.…”

“…The microtubule cytoskeleton is involved in mechanosensation, particularly touch responses (Bounoutas et al, 2009; Tanner et al, 1998; Zhang et al, 2015), and mutations in mouse αTAT1 and C. elegans mec-17 and atat-2 reduce mechanosensitivity (Morley et al, 2016; Shida et al, 2010; Topalidou et al, 2012). In Drosophila , gentle touch activates the TRP channel NOMPC, which relies on microtubule interactions for gating (Zhang et al, 2015), in c3da neurons to elicit stereotyped behaviors, including backward locomotion and turning (Kernan et al, 1994).…”

“…These results demonstrate that although dTat plays a minor role in c4da neuron dendrite development, it is not broadly required for mechanosensory neuron morphogenesis. Similarly, mouse Atat1 (Morley et al, 2016) and C. elegans mec-17 (Akella et al, 2010; Shida et al, 2010) are largely dispensable for sensory neuron morphogenesis, suggesting that the wide-ranging effects of dTAT on mechanosensation are likely caused by other mechanisms.…”

“…We next examined whether dTAT regulates cellular rigidity, which could contribute to dTat mutant mechanosensation defects. Loss of the microtubule acetylase α-tubulin N -acetyltransferase 1 (ATAT1) results in increased cellular rigidity of cultured mouse DRG neurons (Morley et al, 2016). To test whether this biophysical function was conserved in Drosophila , we used atomic force microscopy (AFM) to examine the elastic moduli of dTAT-depleted S2 cells and compared them to control-treated cells.…”

The tubulin code at a glance

“…Acetylation has been associated with stable MTs and thus used as a marker for MT stability. So far, it has been shown to have a role in the maturation of megakaryocytes and platelet formation (IancuRubin et al, 2012;Sadoul et al, 2012) and to be essential for touchsensing in mice (Morley et al, 2016) and C. elegans (Topalidou et al, 2012).…”