Using fruit flies, UCSF researchers uncover the molecular basis of our most mysterious physical sense.
Stroke the soft body of a newborn fruit fly larva very gently with an eyelash and it will change its movement in response. That simple behavioral test helped researchers at the University of California, San Francisco (UCSF) identify key cells and molecules that underlie the sensation of gentle touch, one of the most basic yet least understood of our senses.
Gentle touch shapes human experience from the first caresses a newborn receives to comforting contact throughout life. Despite its importance, the molecular details of how organisms detect light mechanical stimuli have remained elusive. In a paper published online in Nature, the UCSF team describes the specific nerve cells and an essential ion channel that confer gentle-touch sensitivity in Drosophila larvae.
The researchers pinpointed a subset of peripheral sensory neurons called class III multidendritic neurons as the primary carriers of gentle-touch signals to the larval brain. At the tips of these neurons they found high concentrations of a protein called NOMPC (No mechanoreceptor potential C). Experimental evidence shows that NOMPC is critical for sensing gentle touch: flies lacking functional NOMPC are insensitive to eyelash stroking, and adding NOMPC to neurons that normally do not detect light touch gives those neurons the ability to respond.
“NOMPC is sufficient to confer sensitivity to gentle touch,” said Yuh Nung Jan, PhD, professor of physiology, biochemistry and biophysics and a Howard Hughes Medical Institute investigator at UCSF, who led the study with Lily Jan, PhD. The findings illuminate a core component of mechanotransduction—the process by which mechanical forces become electrical signals in the nervous system.
The work offers a clearer picture of how gentle touch is detected at the cellular and molecular levels. The study demonstrates that special peripheral nerve endings house sensor molecules that open in response to mechanical deformations of the skin. When the NOMPC channel opens, ions enter the neuron and generate an electrical signal; if the signal is strong enough, the neuron fires and the brain registers the sensation of light touch.
Although the study identifies NOMPC as a major mechanotransduction channel in fruit flies, several important questions remain. The precise mechanical sensing mechanism of NOMPC—how force is translated into channel opening—and the identity of the corresponding human channels that mediate gentle touch in people are still unknown. The UCSF team emphasized that their discovery provides a foundation for future work addressing these gaps.
Why is Touch Still Such a Mystery?
Compared with senses such as vision and taste, the molecular basis of gentle touch has been harder to define. Researchers long suspected that specialized peripheral nerve fibers and molecules at their endings detect skin movement and convert it into electrical signals. What was missing was a clear identification of the nerves and the molecular channels responsible for light mechanical sensitivity.
This study fills that gap in Drosophila by defining the specific neuron class and by identifying NOMPC as a bona fide mechanotransduction channel for gentle touch. The discovery was not the result of a targeted search for touch receptors, but rather came from detailed study of neuronal development. The investigators observed that class III multidendritic neurons consistently form spiky dendritic arbors at the body wall. Those structures proved to be the sites where NOMPC concentrates and where gentle-touch sensing occurs.
Using genetic approaches, the researchers demonstrated that flies engineered with a nonfunctional NOMPC gene do not respond to gentle stroking, while ectopic expression of NOMPC in other neurons is sufficient to produce touch sensitivity. These experiments establish NOMPC both as necessary and sufficient for light-touch mechanosensation in the larval system.
End of UCSF press release
From the first author of the research paper
Zhiqiang Yan’s own words about the research:
Understanding how organisms perceive mechanical stimuli at the molecular level is a fundamental question in biology. We used Drosophila larvae to tackle this challenge and identified a eukaryotic ion channel that can be activated by mechanical force in a heterologous expression system and is required for gentle-touch mechanotransduction in vivo. It was surprising that this single protein can act as a mechanical sensor, since prior models often envisioned more complex, multi-component assemblies.
We found that a class of multidendritic neurons that tile the larval body wall detect the light touch of an eyelash. We identified a channel from the Transient Receptor Potential (TRP) family that is specifically required for this sensation in those neurons, and we showed that the channel alone is a functional mechanotransduction unit. Our results also suggest that different mechanosensitive channels may serve distinct roles for gentle versus noxious mechanical stimuli.
Notes about this neuroscience research
Funding: This work was supported by the National Institutes of Health (grants R37NS040929 and 5R01MH084234), the Howard Hughes Medical Institute, and two Long-Term Fellowships from the Human Frontier Science Program.
Contacts: Zhiqiang Yan, Ph.D. – Jan Lab, Howard Hughes Medical Institute and University of California, San Francisco; Jason Socrates Bardi – University of California, San Francisco.
Sources: University of California, San Francisco press release and research details submitted by Zhiqiang Yan, Ph.D., the paper’s first author.
Image Source: Tickle image by Kyle Flood, credited via Wikimedia Commons.
Original Research: Study published as “Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation” by Zhiqiang Yan, Wei Zhang, Ye He, David Gorczyca, Yang Xiang, Li E. Cheng, Shan Meltzer, Lily Yeh Jan and Yuh Nung Jan in Nature (online).