Turnover and activity-dependent transcriptional control of NompC in the Drosophila ear

Abstract

Across their lives, biological sensors maintain near-constant functional outputs despite countless exogenous and endogenous perturbations. This sensory homeostasis is the product of multiple dynamic equilibria, the breakdown of which contributes to age-related decline. The mechanisms of homeostatic maintenance, however, are still poorly understood. The ears of vertebrates and insects are characterized by exquisite sensitivities but also by marked functional vulnerabilities. Being under the permanent load of thermal and acoustic noise, auditory transducer channels exemplify the homeostatic challenge. We show that (1) NompC-dependent mechanotransducers in the ear of the fruit fly Drosophila melanogaster undergo continual replacement with estimated turnover times of 9.1 hr; (2) a de novo synthesis of NompC can restore transducer function in the adult ears of congenitally hearing-impaired flies; (3) key components of the auditory transduction chain, including NompC, are under activity-dependent transcriptional control, likely forming a transducer-operated mechanosensory gain control system that extends beyond hearing organs.

Physiological changes throughout an insect ear due to age and noise - A longitudinal study

“…We found a decrease in maximal nerve response directly after noise exposure ( Figure 4 Di, Div). This is similar to a decrease in nerve response in Drosophila ( Boyd-Gibbins et al., 2021 ) and the first wave of auditory brainstem responses (ABRs) and compound action potentials after noise exposure in mice ( Kujawa and Liberman, 2009 ; Chuang et al., 2014 ) and rats ( Tagoe et al., 2014 ). Noise-exposed locusts recovered their maximal nerve response within 24 h after first noise exposure but then the auditory nerve response decreased again at 48 h later ( Figure 4 Di-Diii), a 48 h pattern repeated after the second noise exposure on day 4 (Div-Dvi).…”

“…The physiological and anatomical changes that co-occur with hearing loss present at multiple levels of the auditory system. This stretches from the middle ear and tympanum ( Etholm and Belal, 1974 ; Ruah et al., 1991 ; Rolvien et al., 2018 ), to the inner ear supporting cells ( Thorne and Gavin, 1985 ; Shi and Nuttall, 2003 ) and auditory receptors ( Keithley and Feldman, 1982 ; Liberman and Beil, 1978 ; Bohne and Harding, 2000 ; Wu et al., 2019 ; Jeng et al., 2020 ; Boyd-Gibbins et al., 2021 ) including their synapses to the auditory nerve ( Kujawa and Liberman, 2009 , 2015 ; Wu et al., 2019 ) and the central nervous system where sound is processed ( Fetoni et al., 2013 ). The most profound and best quantified change in the auditory system is loss of hair cells ( Coleman, 1976 ; Keithley and Feldman, 1982 ; Bhattacharyya and Dayal, 1985 ; Dayal and Bhattacharyya, 1986 ; Li and Hultcranz, 1994 ; Dixon and Arndt, 1971 ; Pinheiro et al., 1973 ; Clark et al., 1974 ; Moody et al., 1978 ).…”

Physiological Changes Throughout an Insect Ear Due to Age and Noise - A Longitudinal Study

“…In response to noise the tympanal displacements of the desert locust transiently decrease 24 hours after noise exposure but remain unaffected directly after or 48 hours after noise exposure. In the fruit fly noise up-shifts and sharpens the mechanical tuning of its sound-capturing antennae (Boyd-Gibbins et al, 2021). This is due to changes in the active mechanical output of its motile auditory receptors.…”

“…The physiological and anatomical changes that co-occur with hearing loss present at multiple levels of the auditory system. This stretches from the middle ear and tympanum (Etholm and Belal, 1974;Ruah et al, 1991;Rolvien et al, 2018), to the inner ear supporting cells (Thorne and Gavin 1984;Shi & Nuttall, 2003) and auditory receptors (Keithley and Feldman, 1982;Liberman and Beil, 1978;Bohne and Harding, 2000;Wu et al, 2019;Jeng et al, 2020;Boyd-Gibbins et al, 2021) including their synapses to the auditory nerve Liberman, 2009, 2015;Wu et al, 2019) and the central nervous system where sound is processed (Fetoni et al, 2013). The most profound and best quantified change in the auditory system is loss of hair cells (Coleman, 1976;Keithley and Feldman, 1982;Bhattacharyya and Dayal, 1985;Dayal and Bhattacharyya, 1986;Li and Hultcrantz, 1994;Dixon and Ward, 1971;Pinheiro et al, 1973;Clark et al, 1974;Moody et al, 1978).…”

Ciliary membrane, localised lipid modification and cilia function

“…The receptor turnover has complex dynamics and often varies according to the cilia type. For example, the TRP channel NompC, enriched in the nearly 3 μm long OS of the bipartite chordotonal cilium of Drosophila (Park et al, 2013), is estimated to turnover in nearly 9 h (Boyd-Gibbins et al, 2021). Similarly, the level of odour receptor coreceptor (Orco), exclusively located in the OS of Drosophila olfactory cilia (Benton et al, 2006;Jana et al, 2011Jana et al, , 2021, doubles in two episodic phases lasting for less than 2 h immediately after the adult eclosion (Jana et al, 2021).…”