title: Polarity in migrating neurons is related to a mechanism analogous to cytokinesis.
abstract: 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.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Falnikar
authors.forename: Shubha
authors.initials: S
authors.lastname: Tole
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Judy S
authors.initials: JS
authors.lastname: Liu
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D048749:Cytokinesis; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D020690:GTPase-Activating Proteins; C115995:mgcRacGAP; D016547:Kinesins