Function of Ezrin-Radixin-Moesin Proteins in Migration of Subventricular Zone-Derived Neuroblasts Following Traumatic Brain Injury

Abstract

Throughout life, newly generated neuroblasts from the subventricular zone migrate toward the olfactory bulb through the rostral migratory stream. Upon brain injury, these migrating neuroblasts change their route and begin to migrate toward injured regions, which is one of the regenerative responses after brain damage. This injury-induced migration is triggered by stromal cell-derived factor 1 (SDF1) released from microglia near the damaged site; however, it is still unclear how these cells transduce SDF1 signals and change their direction. In this study, we found that SDF1 promotes the phosphorylation of ezrin-radixin-moesin (ERM) proteins, which are key molecules in organizing cell membrane and linking signals from the extracellular environment to the intracellular actin cytoskeleton. Blockade of ERM activation by overexpressing dominant-negative ERM (DN-ERM) efficiently perturbed the migration of neuroblasts. Considering that DN-ERM-expressing neuroblasts failed to maintain proper migratory cell morphology, it appears that ERM-dependent regulation of cell shape is required for the efficient migration of neuroblasts. These results suggest that ERM activation is an important step in the directional migration of neuroblasts in response to SDF1-CXCR4 signaling following brain injury. STEM CELLS 2013;31:1696-1705