Actin waves transport RanGTP to the neurite tip to regulate non-centrosomal microtubules in neurons

Abstract

Microtubules (MTs) are the most abundant cytoskeleton in neurons, and control multiple facets of their development. While the MT-organizing center (MTOC) in mitotic cells is typically located at the centrosome, the MTOC in neurons switches to non-centrosomal sites. A handful of cellular components have been shown to promote non-centrosomal MT (ncMT) formation in neurons, yet the regulation mechanism remains unknown. Here, we demonstrate that the small GTPase Ran is a key regulator of ncMTs in neurons. Using an optogenetic tool that enables light-induced local production of RanGTP, we demonstrate that RanGTP promotes ncMT plus-end growth along the neurite. Additionally, we discovered that actin waves drive the anterograde transport of RanGTP. Pharmacological disruption of actin waves abolishes the enrichment of RanGTP and reduces growing ncMT plus-ends at the neurite tip. These observations identify a novel regulation mechanism for ncMTs and pinpoint an indirect connection between the actin and MT cytoskeletons in neurons.