title: The microtubule-based cytoskeleton is a component of a mechanical signaling pathway in fly campaniform receptors.
abstract: In mechanoreceptors, mechanical stimulation by external forces leads to the rapid opening of transduction channels followed by an electrical response. Despite intensive studies in various model systems, the molecular pathway by which forces are transmitted to the transduction channels remains elusive. In fly campaniform mechanoreceptors, the mechanotransduction channels are gated by compressive forces conveyed via two rows of microtubules that are hypothesized to be mechanically reinforced by an intervening electron-dense material (EDM). In this study, we tested this hypothesis by studying a mutant fly in which the EDM was nearly absent, whereas the other ultrastructural elements in the mechanosensitive organelle were still present at 50% (or greater) of normal levels. We found that the mechanosensory response in this mutant was reduced by 90% and the sensitivity by at least 80%. To test whether loss of the EDM could lead to such a reduction in response, we performed a mechanical analysis and estimated that the loss of the EDM is expected to greatly decrease the overall rigidity, leading to a marked reduction in the gating force conveyed to the channel. We argue that this reduction in force, rather than the reduction in the number of transduction channels, is primarily responsible for the nearly complete loss of mechanosensory response observed in the mutant fly. Based on these experiments and analysis, we conclude that the microtubule-based cytoskeleton (i.e., microtubules and EDM) is an essential component of the mechanical signaling pathway in fly campaniform mechanoreceptor.
authors.affiliation: Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Johnson
authors.initials: J
authors.lastname: Madrid
authors.affiliation: Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut. Electronic address: jonathon.howard@yale.edu.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Howard
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism*; D004583:Electrons; D008465:Mechanoreceptors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D008870:Microtubules / Q000378:metabolism*; D008959:Models, Neurological