Microtubule Acetylation Is Required for Mechanosensation in Drosophila
Connie Yan,
Fei Wang,
Yun Peng,
Claire R. Williams,
Brian Jenkins,
Jill Wildonger,
Hyeon-Jin Kim,
Jonathan B. Perr,
Joshua C. Vaughan,
Megan E. Kern,
Michael R. Falvo,
E. Timothy O’Brien, III,
Richard Superfine,
John C. Tuthill,
Yang Xiang,
Stephen L. Rogers,
Jay Z. Parrish
Affiliations
Connie Yan
Department of Biology, University of Washington, Seattle, WA 98195, USA
Fei Wang
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Yun Peng
Department of Biology, University of Washington, Seattle, WA 98195, USA
Claire R. Williams
Department of Biology, University of Washington, Seattle, WA 98195, USA
Brian Jenkins
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA
Jill Wildonger
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA
Hyeon-Jin Kim
Department of Chemistry, University of Washington, Seattle, WA 98195, USA
Jonathan B. Perr
Department of Chemistry, University of Washington, Seattle, WA 98195, USA
Joshua C. Vaughan
Department of Chemistry, University of Washington, Seattle, WA 98195, USA; Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA
Megan E. Kern
Department of Physics & Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA
Michael R. Falvo
Department of Physics & Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA
E. Timothy O’Brien, III
Department of Physics & Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA
Richard Superfine
Department of Applied and Physical Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA
John C. Tuthill
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA
Yang Xiang
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Stephen L. Rogers
Department of Biology, Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA; Corresponding author
Jay Z. Parrish
Department of Biology, University of Washington, Seattle, WA 98195, USA; Corresponding author
Summary: 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. : Yan et al. identify the major microtubule acetylase in Drosophila and show that the enzyme and microtubule acetylation broadly control mechanosensation, but not other sensory modalities. Acetylation is required for mechanosensation by the TRP channel NOMPC, and possibly other channels, by virtue of its effects on microtubule mechanical stability and/or dynamics. Keywords: Drosophila, mechanosensation, microtubule acetylation, TRP channel, somatosensory neuron
