Regulation of Mechanosensation inC. elegansthrough Ubiquitination of the MEC-4 Mechanotransduction Channel

Abstract

In Caenorhabditis elegans, gentle touch is sensed by the anterior (ALM and AVM) and posterior (PLM) touch receptor neurons. Anterior, but not posterior, touch is affected by several stress conditions via the action of AKT kinases and the DAF-16/FOXO transcription factor. Here we show that a ubiquitination-dependent mechanism mediates such effects. AKT-1/AKT kinase and DAF-16 alter the transcription of mfb-1, which encodes an E3 ubiquitin ligase needed for the ubiquitination of the mechanosensory channel subunit MEC-4. Ubiquitination of MEC-4 reduces the amount of MEC-4 protein in the processes of ALM neurons and, consequently, the mechanoreceptor current. Even under nonstress conditions, differences in the amount of MFB-1 appear to cause the PLM neurons to be less sensitive to touch than the ALM neurons. These studies demonstrate that modulation of surface mechanoreceptors can regulate the sensitivity to mechanical signals.

Tissue mechanics govern the rapidly adapting and symmetrical response to touch

“…The average adaptation time constant of MeT currents evoked by large, displacement-clamped mechanical loads was 22 ms (n = 2, soft worms, x t = 5 μm). These values are similar to those reported previously using open-loop mechanical stimulation methods (12,13,44,53). Importantly, these adaptation rates are decoupled from the rate of stimulation because the closed-loop rise time was much faster than MeT current adaptation in all cases, varying from 4 ms (n = 2, stiff worms under force clamp, F = 5 μN) to 6 ± 2 ms (mean ± SD, n = 19, soft worms under force clamp, F = 1 μN) to 8 ms (n = 2, soft worms under displacement clamp, x t = 5 μm).…”

“…Whether delivering force or displacement, systems for mechanical stimulation used by us and others to investigate MeT currents in C. elegans have lacked feedback control (12,13,16,18,20,44). Similar open-loop systems are in widespread use for analysis of mammalian somatosensory neurons (45,46) and cannot distinguish between changes in stimulus amplitude and channel adaptation, regardless of whether stimuli are reported as applied force or stimulator displacement.…”

Composition and Control of a Deg/ENaC Channel during Presynaptic Homeostatic Plasticity

“…This family includes sodium leak channels (Chalfie, 2009), channels gated by low pH (Boiko et al, 2012; Du et al, 2014), chemoreceptors (Lin et al, 2005; Mast et al, 2014; Toda et al, 2012), and mechanoreceptors (Chen and Chalfie, 2015; Goodman et al, 2002; Gorczyca et al, 2014; Guo et al, 2014). Beyond this, a growing list of ligands has been shown to activate these channels including small neuropeptides and opioid peptides (Askwith et al, 2000).…”

Identification of Nonviable Genes Affecting Touch Sensitivity inCaenorhabditis elegansUsing Neuronally Enhanced Feeding RNA Interference

“…The plasmid mec-17p :: rfp and the entry clones containing mec-3p and unc-54 3′utr were described by Chen and Chalfie (2015). txdc-9 genomic sequence was amplified using the primers GGGGACAAGTTTGTACAAAAAAGCAGGCTTAatggccgctaatattcaacagcagt and GGGGACCACTTTGTACAAGAAAGCTGGGTGctaccaatcctcttcgttatcgtactcc.…”