PROPRIOCEPTION Together, These Findings Provide Compelling Evidence That TRPN1 Is One of the Elusive Force-Gated Sensory Sensational Mechanics Channels

RESEARCH HIGHLIGHTS

Nature Reviews Neuroscience | AOP, published online 15 September 2010; doi:10.1038/nrn2922

PROPRIOCEPTION Together, these findings provide compelling evidence that TRPN1 is one of the elusive force-gated sensory Sensational mechanics channels. Although this channel is not expressed in mammals, several Many senses that are based on mech- contractions propagating from other TRP family members are, and anosensation, such as proprioception posterior to anterior segments gener- these studies represent an important and touch, are known to be mediated ated Ca2+ signals in sensory neurons advance in this challenging field. by force-sensitive ion channels, but the that were relayed to the VNC, Katie Kingwell identity of these channels has proved representing a sensory response to elusive. Now, two papers in Neuron muscle contractions. In TRPN1-null ORIGINAL RESEARCH PAPERS Cheng, L. E. report findings that directly implicate preparations, this segmental propaga- et al. The role of the TRP channel NompC in Drosophila larval and adult locomotion. Neuron 2+ transient receptor potential cation tion of the Ca signal in the VNC was 67, 373–380 (2010) | Kang, L. et al. C. elegans TRP channel N1 (TRPN1; also known as abolished. Interestingly, this function family protein TRP‑4 is a pore‑forming subunit of a native mechanotransduction channel. Neuron NompC and TRP4) in mechanosensa- of TRPN1 in proprioception seems 67, 381–391 (2010) tion by fruitflies and nematode worms. to be conserved, as previous work in FURTHER READING Li, W. et al. A C. elegans Cheng et al. showed the impor- Caenorhabditis elegans also revealed stretch receptor neuron revealed by a mechanosensitive TRP channel homologue. tance of TRPN1 for proprioception a crucial role for the receptor in Nature 440, 684–687 (2006) in Drosophila melanogaster. Using a this process. green fluorescent protein construct, Kang et al. focused on the the authors showed expression of C. elegans ciliated mechanosensory the channel in subsets of peripheral neuron known as CEP, which is sensory neurons that had previously located in the nose tip of the worm been implicated in coordinating and is involved in the slowing of locomotion. movement in response to touching TRPN1-null larvae crawled food particles. Removing the cuticle more slowly than wild-type larvae, on the worm head to expose the CEP suggesting impaired proprioception cell body enabled whole-cell patch given the loss of TRPN1 in sensory clamp recordings during mechanical neurons, and TRPN1-null adult flies stimulation of the nose tip. The rapid exhibited uncoordinated leg and activation and latency times of the wing movements, and were unable recorded mechanoreceptor current to walk or fly. These defects were suggested that it is mediated by a rescued by expression of TRPN1 mechanically gated channel. This under the control of sensory-neuron- current and the movement-slowing specific promoters. response was absent in mutant To directly observe the in vivo worms lacking TRPN1 and was effects of TRPN1, the authors rescued by re-expression of the chan- expressed a Ca2+ sensor in a larval nel. Crucially, to show that TRPN1 preparation that maintains peristaltic is directly responsible for the mech- muscle contractions. In fruitflies, anoreceptor current, the authors sensory neurons in each body mutated key residues in the putative segment project to the correspond- pore-forming domain of the channel ing segment of the ventral nerve protein and showed that this changed cord (VNC) in the CNS. Muscle the cation-selectivity of the current.