title: Reelin acts as a stop signal for radially migrating neurons by inducing phosphorylation of n-cofilin at the leading edge.
abstract: The extracellular matrix protein Reelin, secreted by Cajal-Retzius (CR) cells in the marginal zone (MZ) of the cerebral cortex, is important for neuronal migration during development. Two lipoprotein receptors for Reelin have been identified, apolipoprotein E receptor 2 (ApoER2) and the very low-density lipoprotein receptor (VLDLR). The binding of Reelin to these receptors induces tyrosine phosphorylation of an adapter protein, disabled 1 (Dab1) by src family kinases (SFKs). In the Reelin-deficient mutant reeler, cortical lamination is inverted with many neurons invading the marginal zone and others that are unable to migrate to their destinations and accumulate underneath their predecessors, suggesting a role for Reelin signaling in dynamic cytoskeletal reorganization. At present these effects of Reelin are poorly understood. In our recent study, we showed that Reelin induces serine3 phosphorylation of n-cofilin, an actin-depolymerizing protein promoting the disassembly of F-actin. Phosphorylation of cofilin renders it unable to depolymerize F-actin, thus stabilizing the cytoskeleton. We provided evidence for ApoER2, Dab1, SFKs and phosphatidylinositol-3-kinase (PI3K) to be involved in Reelin-induced cofilin phosphorylation. We found that phosphorylation of cofilin occurs in the leading processes of radially migrating neurons as they grow towards the Reelin-containing marginal zone. By cofilin phosphorylation, Reelin may act as a stop signal for radially migrating neurons.
authors.affiliation: Institut für Anatomie und Zellbiologie; Albert-Ludwigs-Universität Freiburg; Freiburg, Germany.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chai
authors.forename: Eckart
authors.initials: E
authors.lastname: Förster
authors.forename: Shanting
authors.initials: S
authors.lastname: Zhao
authors.forename: Hans H
authors.initials: HH
authors.lastname: Bock
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher