Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

Abstract

Summary: As an essential step for brain morphogenesis, neurons migrate via mechanical interactions with components of their environment such as neighboring cells and the extracellular matrix. However, the molecular mechanism by which neurons exert forces on their environment during migration remains poorly understood. Here, we show that shootin1b is expressed in migrating mouse olfactory interneurons and accumulates at their leading process growth cone. We demonstrate that shootin1b, by binding to cortactin and L1-CAM, couples F-actin retrograde flow and the adhesive substrate as a clutch molecule. Shootin1b-mediated clutch coupling at the growth cone generates traction force on the substrate, thereby promoting leading process extension and subsequent somal translocation of olfactory interneurons. Furthermore, loss of shootin1 causes abnormal positioning of the interneurons and dysgenesis of the olfactory bulb. Our findings indicate that shootin1b plays a key role in force-driven leading process extension, which propels the migration of olfactory interneurons during olfactory bulb formation. : Minegishi et al. use gene knockout, protein interaction assays, force microscopy, speckle imaging, and migration assays to analyze the molecular mechanics driving neuronal migration in vivo. Their data demonstrate that shootin1b mediates a mechanical clutch to produce force for the migration of olfactory interneurons in the brain. Keywords: neuronal migration, olfactory bulb, interneuron, leading process, growth cone, shootin1, L1-CAM, clutch molecule