A channel for gentle touch sensation was found in Drosophila

Touch sensation is essential for behaviors ranging from environmental exploration to social interaction, but the underlying mechanisms are largely unknown. Here we found that class III dendritic arborization (da) neurons of Drosophila larvae are touch sensitive and contribute to gentle touch sensation. We further identify NOMPC (no mechanoreceptor potential C), as a pore-forming subunit of a mechanotransduction channel for gentle touch.

HFSP Long-Term Fellow Zhiqiang Yan and colleagues
authored on Fri, 21 December 2012

Mechanosensation requires the transformation of mechanical stimuli into neuronal signals. Our senses of touch, sound and gravity rely on mechanosensation. Notwithstanding the importance of mechanosensation, its cellular and molecular mechanisms are the least well understood among the different sensory modalities. Unlike other senses such as vision, olfaction and taste, for which there is a wealth of knowledge about the sensory transduction processes, the molecules (channels) that transduce the mechanical stimuli remain largely unidentified because of various technical difficulties.

Figure: Class III dendritic arborization neurons tile the larval body wall.

For a channel to be considered a transducer of mechanical stimuli, Arnadottir and Chalfie (2010) have put forward 4 criteria that must apply to mechanosensitive channels: First, the channel must have appropriate temporal and spatial expression patterns within the mechanosensory organ. Second, the channel must be required for the animal’s response to mechanical stimuli. Third, alteration of the properties of the channel protein should alter the properties of the mechanical response. Fourth, heterologous expression of the channel should demonstrate that it could be gated mechanically.

Many candidate mechanosensitive ion channels have been identified over the years, including degenerin/epithelial sodium channels (DEG/ENaC), two pore domain potassium channels and transient receptor potential (TRP) channels. However, not a single eukaryotic channel thought to be involved in mechanosensation has been reported to satisfy all four criteria until this year. For example, although there is compelling evidence supporting the DEG/ENaC channels’ role in mechanotransduction in C. elegans touch sensory neurons, heterologous expression of these channels demonstrating that they could be mechanically gated has not yet been achieved. This fourth criterion has been difficult to satisfy; one plausible explanation is that the heterologous expression studies often have not achieved the condition for proper channel tethering essential for mechanical gating. Another emerging candidate is NOMPC, a Drosophila TRP channel that is essential for mechanotransduction in external sensory neurons in the bristles of adult Drosophila and is also important for hearing and larval locomotion. There is also strong evidence suggesting that TRP-4, the C. elegans homologue of Drosophila NOMPC, is a pore-forming subunit of a mechanotransduction channel. Once again, what has been lacking is the heterologous expression of these channels from Drosophila or C. elegans and demonstration of mechanical gating of such heterologously expressed channels.

Recently, a very strong case has been made for Drosophila Piezo (DmPiezo) as a mechanosensitive channel mediating mechanical nociception in Drosophila larvae (Ref 1). In this study, all four criteria appear to be satisfied. DmPiezo is expressed in the class IV dendritic arborization (da) neurons that mediate nociception, and it is required for those neurons’ ability to produce mechanically activated current and the larva’s proper behavioral response to noxious mechanical stimulation. Importantly, heterologous expression of DmPiezo could produce mechanically gated current.

Similar to vertebrate animals, Drosophila has a rich repertoire of mechanosensation including hearing, gravity sensing, proprioception, mechanical nociception and gentle touch sensing, which may involve different sensory neurons of the peripheral nervous system (PNS). Whereas class IV da neurons and DmPiezo are essential for mechanical nociception, they are not required for gentle touch sensing . It is therefore of interest to address the following questions: Which type(s) of sensory neurons in the Drosophila PNS function to sense gentle touch? What are the mechanotransduction channels used for this function?

By combining behavioral assays, electrophysiological recording and calcium imaging, we have identified class III da neurons as a major mediator of gentle touch sensation for Drosophila larvae. Not only did class III da neurons display vigorous responses to gentle touch, the behavioral response to touch was eliminated by silencing these neurons. Class III da neurons along with class IV da neurons are the only two types of sensory neurons that tile the larval body wall. Whereas class IV da neurons sense harsh mechanical stimuli (see Ref 1 and Ref 2 below), class III da neurons sense gentle touch (this work). Having found that NompC is highly expressed in class III da neurons by immunostaining, we have uncovered an essential role of NompC for sensing gentle touch in these neurons. Moreover, ectopic expression of NompC in class IV and class I da neurons, which normally do not respond to mechanical force, conferred the capacity of robust responses to gentle touch. Finally, expression of NompC in Drosophila S2 cells was sufficient to generate mechanically gated current, thereby allowing us to study the biophysical properties of NompC channels in a heterologous system. Importantly, point mutations of the predicted pore region of NOMPC altered its channel properties including the ion selectivity. Taken together, this study demonstrates that NompC is a pore-forming subunit of a mechanotransduction channel functioning in class III da neurons to sense gentle touch.

Reference

Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Zhiqiang Yan,  Wei Zhang, Ye He, David Gorczyca, Yang Xiang,Li E. Cheng, Shan Meltzer,Lily Yeh Jan , Yuh Nung Jan. Nature (2012) doi:10.1038/nature11685.

Other References

Ref 1: The role of Drosophila Piezo in mechanical nociception. Kim, S. E., B. Coste, et al. (2012). Nature 483(7388): 209-212.

Ref 2: Pickpocket is a DEG/ENaC protein required for mechanical nociception in Drosophila larvae. Zhong, L., R. Y. Hwang, et al. (2010). Curr Biol 20(5): 429-434.

Pubmed link

Link to Nature paper