title: 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.
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.|Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
authors.forename: Shane J
authors.initials: SJ
authors.lastname: Morley
authors.affiliation: Centre for Integrative Neuroscience, Tuebingen, Germany.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.|Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
authors.forename: Loredana
authors.initials: L
authors.lastname: Iovino
authors.affiliation: Istituto Officina dei Materiali-CNR, Trieste, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Andolfi
authors.affiliation: Centre for Integrative Neuroscience, Tuebingen, Germany.
authors.forename: Da
authors.initials: D
authors.lastname: Guo
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Nereo
authors.initials: N
authors.lastname: Kalebic
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Castaldi
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Tischer
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Portulano
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bolasco
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Kalyanee
authors.initials: K
authors.lastname: Shirlekar
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Fusco
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Asaro
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fermani
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Mayya
authors.initials: M
authors.lastname: Sundukova
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Matti
authors.affiliation: Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Reymond
authors.affiliation: Consiglio Nazionale delle Ricerche, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: De Ninno
authors.affiliation: Consiglio Nazionale delle Ricerche, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Businaro
authors.affiliation: Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
authors.forename: Kai
authors.initials: K
authors.lastname: Johnsson
authors.affiliation: Istituto Officina dei Materiali-CNR, Trieste, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lazzarino
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Jonas
authors.identifier: 0000-0002-6640-9250
authors.initials: J
authors.lastname: Ries
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Yannick
authors.identifier: 0000-0001-8027-1836
authors.initials: Y
authors.lastname: Schwab
authors.affiliation: Centre for Integrative Neuroscience, Tuebingen, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: EMBL Mouse Biology Unit, Monterotondo, Italy.|Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
authors.forename: Paul A
authors.identifier: 0000-0001-7954-5166
authors.initials: PA
authors.lastname: Heppenstall
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017353:Gene Deletion; D051379:Mice; D008868:Microtubule Proteins; D009475:Neurons, Afferent / Q000201:enzymology* / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D014110:Touch; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008868:Microtubule Proteins; D014404:Tubulin; D000123:Acetyltransferases; C583619:ATAT1 protein, mouse
keywords: acetylation; microtubules; mouse; neuroscience; sensory neuron