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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Vydáno v:Neuron (Cambridge, Mass.) Ročník 76; číslo 2; s. 353
Hlavní autoři: Sekine, Katsutoshi, Kawauchi, Takeshi, Kubo, Ken-Ichiro, Honda, Takao, Herz, Joachim, Hattori, Mitsuharu, Kinashi, Tatsuo, Nakajima, Kazunori
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 18.10.2012
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ISSN:1097-4199, 1097-4199
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Abstract 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.
AbstractList 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.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.
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.
Author Kubo, Ken-Ichiro
Herz, Joachim
Kawauchi, Takeshi
Honda, Takao
Kinashi, Tatsuo
Nakajima, Kazunori
Sekine, Katsutoshi
Hattori, Mitsuharu
Author_xml – sequence: 1
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  surname: Sekine
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  organization: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan
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  givenname: Takeshi
  surname: Kawauchi
  fullname: Kawauchi, Takeshi
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  givenname: Ken-Ichiro
  surname: Kubo
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  givenname: Takao
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  fullname: Kinashi, Tatsuo
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  surname: Nakajima
  fullname: Nakajima, Kazunori
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23083738$$D View this record in MEDLINE/PubMed
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Snippet Birthdate-dependent neuronal layering is fundamental to neocortical functions. The extracellular protein Reelin is essential for the establishment of the...
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SubjectTerms 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
Title Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin α5β1
URI https://www.ncbi.nlm.nih.gov/pubmed/23083738
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