GSK3β and PKCζ function in centrosome localization and process stabilization during Slit-mediated neuronal repolarization

• DOI: 10.1016/j.mcn.2006.03.003
• Publication Date: 2006-05-07T11:12:53Z
• Authors: Holden Higginbotham; Teruyuki Tanaka; Brendan C. Brinkman; Joseph G. Gleeson
• Keywords: Cell Nucleus; Centrosome; Neurons; 0303 health sciences; Glycogen Synthase Kinase 3 beta; Cell Polarity; Cell Differentiation; Nerve Tissue Proteins; Olfactory Bulb; Cell Line; Glycogen Synthase Kinase 3; Mice; 03 medical and health sciences; Organ Culture Techniques; Cell Movement; Neurites; Animals; Humans; Cues; Cytoskeleton; Protein Kinase C; Glycoproteins

In comparison with other migratory cells, neurons exhibit a unique, highly polarized morphology and a distinctive pattern of movement. This migration consists of a repeating of three distinct phases: neurite outgrowth, movement of the centrosome into the leading process, and translocation of the nucleus towards the centrosome. The direction of movement is under the control of extracellular guidance cues, but mechanisms by which these determine neuronal polarity, centrosome position, and neuronal movement are not well understood. We found that in primary olfactory bulb neuronal precursors, Slit-mediated repolarization consisted of growth of a new process from the previous trailing edge, then reorientation of the centrosome followed by nuclear translocation in the reverse direction. Inhibition of cell polarity factors GSK3beta or PKCzeta resulted in impaired centrosome reorientation and process stabilization. Our findings suggest that activation of cell polarity signaling and positioning of the centrosome ahead of the nucleus are important steps in repolarization in response to guidance cues.