They demonstrated that, like DEG/ENaC currents,

wild-type ASH mechanotransduction currents are amiloride-sensitive and carried primarily by Na+ ions, with suppression potentials exceeding +60 mV. To test whether DEG/ENaCs are necessary for ASH mechanotransduction, Geffeney et al. (2011) analyzed unc-8 and deg-1(u443) mutants ( Savage www.selleckchem.com/products/NVP-AUY922.html et al., 1989). Loss of deg-1, but not unc-8, reduced peak transduction currents by ∼80%. Disrupting both DEG/ENaCs did not further reduce currents. Importantly, voltage-dependent currents were intact, indicating that deg-1 is required specifically for mechanotransduction rather than general membrane excitability. To assess whether deg-1 encodes pore-forming transduction channels, the authors analyzed deg-1 (u506u679) mutants that harbor a point mutation in the second Rigosertib transmembrane domain. In these mutants, transduction currents reversed at ∼0 mV, signifying altered ion selectivity. This mutation also decreased

nose-touch avoidance. Collectively, these data strongly indicate that DEG-1 carries the bulk of ASH mechanotransduction currents. What about osm-9 and ocr-2? These TRP channels are obvious candidates to mediate ASH’s deg-1-independent transduction currents, whose reversal potential (−23 mV) indicates that sodium is not the principle charge carrier. Surprisingly, ASH peak mechanotransduction currents in osm-9 and ocr-2 single and double mutants were similar to wild-type animals. Moreover, mechanotransduction currents in osm-9ocr-2;deg-1 triple mutants were comparable

to those of deg-1 animals, demonstrating that they are not required for minor transduction currents. These data argue against direct involvement of OSM-9/OCR-2 in mechanotransduction. Instead, they must act downstream of DEG-1 since they are essential for ASH-mediated behaviors. This model fits well with the role of TRP channels as signal amplifiers or integrators in other mechanosensory cell types (Figure 1; Arnadóttir and Chalfie, 2010). For example, Nan and Iav, which are essential for sound-evoked responses in Drosophila chordotonal organs, are proposed to control mechanical amplification Sitaxentan downstream of NompC transduction channels ( Figure 1B). Additionally, TRPA1 modulates firing of mechanically evoked responses in mammalian cutaneous afferents ( Figure 1D). The findings presented by Geffeney et al. (2011) lay the groundwork for mechanistic studies of ASH polymodal signaling. Analysis of chemo- and osmotic-induced currents in deg-1 mutants will be necessary to determine if these modalities molecularly segregate. To satisfy a key criterion for mechanotransduction channels, DEG-1 localization to sensory cilia must be shown. Further analysis of the u443 mutation is also needed. Along with disrupting deg-1, this ∼28 kb deletion allele removes an adjacent gene, mec-7, and abolishes behavioral responses to gentle body touch ( Savage et al., 1989).