Polarity in migrating neurons is related to a mechanism analogous to cytokinesis

Migrating neurons are bipolar, with a leading process and a trailing process [1]. The proximal region of the leading process displays a concentration of F-actin that contributes to the advance of the soma and the centrosome [2-7]. Here, we show that kinesin-6, a microtubule-based motor protein best known for its role in cytokinesis, also concentrates in this region. Depletion of kinesin-6 results in multipolar neurons that either are stationary or continuously change their direction of movement. In such neurons, F-actin no longer concentrates in a single process. During cytokinesis, kinesin-6 forms a complex with a Rho-family GTPase-activating protein called MgcRacGAP to signal to the actin cytoskeleton so that cortical movements are concentrated in the cleavage furrow [8-13]. During neuronal migration, MgcRacGap also concentrates in the proximal region of the leading process, and inhibition of its activity results in a phenotype similar to kinesin-6 depletion. We conclude that neuronal migration utilizes a cytoskeletal pathway analogous to cytokinesis, with kinesin-6 signaling through MgcRacGap to the actin cytoskeleton to constrain process number and restrict protrusive activity to a single leading process, thus resulting in a bipolar neuron able to move in a directed fashion.