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

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 &...

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Vydané v:	Neuron (Cambridge, Mass.) Ročník 76; číslo 2; s. 353
Hlavní autori:	Sekine, Katsutoshi, Kawauchi, Takeshi, Kubo, Ken-Ichiro, Honda, Takao, Herz, Joachim, Hattori, Mitsuharu, Kinashi, Tatsuo, Nakajima, Kazunori
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 18.10.2012
Predmet:	Adaptor Proteins, Signal Transducing Analysis of Variance Animals Cell Adhesion - drug effects Cell Adhesion - genetics Cell Adhesion - physiology Cell Adhesion Molecules, Neuronal - drug effects Cell Adhesion Molecules, Neuronal - genetics Cell Adhesion Molecules, Neuronal - metabolism Cell Line, Transformed Cell Movement - drug effects Cell Movement - genetics Cell Movement - physiology Electroporation Embryo, Mammalian Extracellular Matrix Proteins - drug effects Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Female Gene Expression Regulation - drug effects Gene Expression Regulation - genetics Gene Expression Regulation - physiology Green Fluorescent Proteins - genetics Humans Integrin alpha5beta1 - genetics Integrin alpha5beta1 - metabolism Mice Mice, Inbred ICR Mice, Neurologic Mutants Mice, Transgenic Mutation - genetics Nerve Tissue Proteins - drug effects Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurons - drug effects Neurons - physiology Nuclear Proteins Pregnancy Proto-Oncogene Proteins c-crk - metabolism rap1 GTP-Binding Proteins - metabolism Serine Endopeptidases - drug effects Serine Endopeptidases - genetics Serine Endopeptidases - metabolism Signal Transduction - genetics Signal Transduction - physiology Somatosensory Cortex - cytology
ISSN:	1097-4199, 1097-4199
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Popis
Shrnutí:	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 α5β1 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 α5β1. Since fibronectin is localized in the MZ, the activated integrin α5β1 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4199 1097-4199
DOI:	10.1016/j.neuron.2012.07.020