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Publication : Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin α5β1.

First Author  Sekine K Year  2012
Journal  Neuron Volume  76
Issue  2 Pages  353-69
PubMed ID  23083738 Mgi Jnum  J:315273
Mgi Id  MGI:6829968 Doi  10.1016/j.neuron.2012.07.020
Citation  Sekine K, et al. (2012) Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin alpha5beta1. Neuron 76(2):353-69
abstractText  Birthdate-dependent neuronal layering is fundamental to neocortical functions. The extracellular protein Reelin is essential for the establishment of the eventual neuronal alignments. Although this Reelin-dependent neuronal layering is mainly established by the final neuronal migration step called "terminal translocation" beneath the marginal zone (MZ), the molecular mechanism underlying the control by Reelin of terminal translocation and layer formation is largely unknown. Here, we show that after Reelin binds to its receptors, it activates integrin alpha5beta1 through the intracellular Dab1-Crk/CrkL-C3G-Rap1 pathway. This intracellular pathway is required for terminal translocation and the activation of Reelin signaling promotes neuronal adhesion to fibronectin through integrin alpha5beta1. Since fibronectin is localized in the MZ, the activated integrin alpha5beta1 then controls terminal translocation, which mediates proper neuronal alignments in the mature cortex. These data indicate that Reelin-dependent activation of neuronal adhesion to the extracellular matrix is crucial for the eventual birth-date-dependent layering of the neocortex.
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