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Microtubule Acetylation Is Required for Mechanosensation in Drosophila.

Cell reports (2018-10-26)
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, Richard Superfine, John C Tuthill, Yang Xiang, Stephen L Rogers, Jay Z Parrish
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Acetylated Tubulin antibody, Mouse monoclonal, clone 6-11B-1, purified from hybridoma cell culture
Sigma-Aldrich
Anti-α-Tubulin−FITC antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture
Sigma-Aldrich
Biocytin, ≥98% (TLC)
Sigma-Aldrich
Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid