Acetylated tubulin is essential for touch sensation in mice.

Shane J Morley ,Carla Portulano,Laura Castaldi,Mayya Sundukova,Jing Hu,Marco Lazzarino,Luc Reymond,Antonino Asaro,Christian Tischer,Claudia M Fusco,Luca Businaro,Nereo Kalebic,Kai Johnsson,Giulia Bolasco,Yannick Schwab,Federica Fermani,Ulf Matti,Yanmei Qi,Loredana Iovino,Adele De Ninno,Laura Andolfi,Kalyanee Shirlekar,Da Guo,Jonas Ries,Paul A Heppenstall

doi:10.7554/elife.20813

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.

Highlights

Mechanical forces acting upon cells or tissues are propagated into the opening of mechanically gated ion channels such as Piezo2 as the first step in the sense of touch (Abraira and Ginty, 2013; Maksimovic et al, 2014; Ranade et al, 2014; Woo et al, 2014)
We examined whether mechanical sensitivity to punctate stimuli was altered in Atat1cKO mice by applying von Frey filaments of calibrated forces to the hindpaw of mice
We further examined the distribution of acetylated a-tubulin in intact preparations of the peripheral nervous system.Acetylation was enriched under the membrane of axons in the saphenous nerve (Figure 7—figure supplement 1) and apparently at sensory neuron terminal endings in the cornea where mechanotransduction takes place (Figure 7— figure supplement 1, Video 4)

Summary

Introduction

Mechanical forces acting upon cells or tissues are propagated into the opening of mechanically gated ion channels such as Piezo as the first step in the sense of touch (Abraira and Ginty, 2013; Maksimovic et al, 2014; Ranade et al, 2014; Woo et al, 2014). In many cases this process occurs through direct interplay of ion channels with the lipid bilayer.

Methods

Results

Conclusion