Tau Like Proteins Reduce Torque Generation in Microtubule Bundles

Abstract

All animals and plants, even protozoa, have evolved specialized molecular sensors that convert mechanical stress into behavioral responses. The touch receptor neurons (TRNs) in Caenorhabditis elegans respond to gentle body touch and are especially arguably better characterized on a physiological and ultrastructural level than somatosensory neurons in other animals. C. elegans is a unique model organism in which to study the mechanics of neurons due to their simple shapes, the known wiring diagram, transparent body, and a rich repertoire of simple behaviors. As in other animals, neuron morphology is critical for function in C. elegans. We have previously shown that a functional, pre-stressed spectrin network is critical for mechanosensation and neuron stability under body-evoked forces (Krieg, Nat Cell Bio, 2014). How the constituent molecules of these different neurons establish a functional organization and how nanometer sized molecules can determine cell shape in the millimeter scale and enable axons to resist external forces is still not understood. We addressed this question using light, electron and STED microscopy and found that TRNs defects in the organization of the axonal spectrin lattice and microtubule bundles undergo deformations highly similar to a twisted rod under compression. Our data suggests that tau-like proteins minimize microtubule lattice interactions and the prevent torque generation that leads to extreme neuron deformations. These experimental results, together with mechanical modeling of the neuron, suggest that spectrin tension and microtubule bundle mechanics are crucial for stabilizing chiral cytoskeletal networks and produce a specialized cell shape that we propose is critical for neuronal function.