Cytoskeletal mechanisms of axonal contractility

Abstract

Mechanotransduction is likely to be an important mechanism of signalling in thin, elongated cells like neurons. Maintenance of pre-stress or rest tension may facilitate mechanotransduction in these cells. In recent years, functional roles for mechanical tension in neuronal development and physiology are beginning to emerge but the cellular mechanisms regulating neurite tension remain poorly understood. Active contraction of neurites is a potential mechanism of tension regulation. In this study, we have explored cytoskeletal mechanisms mediating active contractility of neuronal axons. We have developed a simple assay where we evaluate contraction of curved axons upon trypsin-mediated detachment. We show that curved axons undergo contraction and straighten upon de-adhesion. Axonal straightening was found to be actively driven by actomyosin contractility, while microtubules may subserve a secondary role. We find that while axons show a monotonous decrease in length upon contraction, subcellularly, the cytoskeleton shows a heterogeneous contractile response. Further, using an assay for spontaneous development of tension without trypsin-induced de-adhesion, we show that axons are intrinsically contractile. These experiments, using novel experimental approaches, implicate the axonal cytoskeleton in tension homeostasis. Our data suggest that while globally the axon behaves as a mechanical continuum, locally the cytoskeleton is remodelled heterogeneously.