Touch as a Matter of Fat: The Phospholipids and DEG/ENaC Channels Needed for Metazoan Touch Sensation

Abstract

Mechano-electrical transduction (MeT) channels are activated by mechanical energy and conduct ions across cell membranes. Such channels enable somatosensory neurons in our skin, joints, and muscles to monitor external touch and self-movement and to detect noxious inputs that initiate pain sensation. They also enable visceral sensory neurons such as baroreceptors to regulate heart function on a beat-by-beat basis. Genetic dissection in roundworms, fruitflies, and mice has led to the identification of many of the proteins that form MeT channels, including members of the TRP family of cation channels, DEG/ENaC sodium channels, and Piezo cation channels. This talk will present evidence establishing that DEG/ENaC sodium channels play crucial roles in both touch and nociception (O'Hagan et al, Nat Neurosci, 11:543, 2005; Geffeney et al, Neuron 71:845, 2011), highlighting aspects of the biophysics of MeT channel activation shared across neurons, species, and protein partners. To learn more about the physical basis of MeT channel activation in living sensory neurons, we are investigating the role of fatty acids and lipids in this process. Through a combination of genetic dissection and chemical complementation, we have identified specific poly-unsaturated phospholipids essential for normal touch sensation. We have also investigated how such lipids contribute to membrane mechanics. Collectively, our results support a model in which mechanosensitivity is a function not only of the proteins that form eukaryotic MeT channels, but also of the surrounding plasma membrane. Support: NIH NS047715; EB006745; AHA and HFSP Postdoctoral Fellowships.