B-Spectrin and the Mechanical Control of the Sense of Touch

Abstract

Many somatosensory neurons have evolved specialized molecular sensors that convert mechanical stress into behavioral responses. The genetics, development and physiology of the touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are especially well characterized and this animal has the particular advantage that the TRNs can be studied both in living animals and dissociated in culture. Like other somatosensory neurons, the TRNs use ion channels to convert mechanical stress into electrical signals and, ultimately, into appropriate behaviors. Whereas the protein partners that form these channels have been known for some time, the nature of the molecular machine important for efficient force transmission from skin to touch receptor neurite is essentially unknown.Using a combination of approaches, we will show that sensation of mechanical forces depends on a continuous, pre-strained spectrin cytoskeleton inside neurons. We observed that mutations in the tetramerization domain of C. elegans β-spectrin (UNC-70), an actin-membrane crosslinker, lead to defective neuron morphologies under compressive stresses in moving animals. We performed AFM force spectroscopy experiments on isolated neurons, laser axotomy and FRET imaging to measure forces across single cells and molecules. Our data indicate that spectrin is held under constitutive tension in living animals, which contributes to an elevated pre-stress in TRNs. Based on these results and data obtained from optogenetic and mechanical stimulation on β-spectrin mutants, we suggest that β-spectrin-dependent pre-tension is required for efficient responses to external mechanical stimuli.