Reelin induces EphB activation
| Autor: | Mario I. Romero-Ortega, Mark Henkemeyer, Timothy Catchpole, Jost Leemhuis, Elisabeth Bouché, Joachim Herz, Petra May, Hans H. Bock, Michael Frotscher |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
hippocampus
neural development Mice chemistry.chemical_compound 0302 clinical medicine Chlorocebus aethiops Reelin Phosphorylation Cerebral Cortex Mice Knockout Neurons Extracellular Matrix Proteins 0303 health sciences Neuronal Plasticity lipoprotein receptor biology Serine Endopeptidases Gene Expression Regulation Developmental tyrosine kinase Signal transducing adaptor protein DAB1 ephrin Cell biology COS Cells Original Article Signal transduction signal transduction Protein Binding Receptor EphB1 Receptor EphB2 Cell Adhesion Molecules Neuronal VLDL receptor Nerve Tissue Proteins signaling crosstalk 03 medical and health sciences Animals Ephrin Molecular Biology LDL-Receptor Related Proteins 030304 developmental biology Binding Sites Tyrosine phosphorylation Cell Biology Embryo Mammalian Protein Structure Tertiary Reelin Protein Receptors LDL nervous system chemistry biology.protein Receptor clustering 030217 neurology & neurosurgery |
| Zdroj: | Cell Research |
| ISSN: | 1748-7838 1001-0602 |
| DOI: | 10.1038/cr.2013.7 |
| Popis: | The integration of newborn neurons into functional neuronal networks requires migration of cells to their final position in the developing brain, the growth and arborization of neuronal processes and the formation of synaptic contacts with other neurons. A central player among the signals that coordinate this complex sequence of differentiation events is the secreted glycoprotein Reelin, which also modulates synaptic plasticity, learning and memory formation in the adult brain. Binding of Reelin to ApoER2 and VLDL receptor, two members of the LDL receptor family, initiates a signaling cascade involving tyrosine phosphorylation of the intracellular cytoplasmic adaptor protein Disabled-1, which targets the neuronal cytoskeleton and ultimately controls the positioning of neurons throughout the developing brain. However, it is possible that Reelin signals interact with other receptor-mediated signaling cascades to regulate different aspects of brain development and plasticity. EphB tyrosine kinases regulate cell adhesion and repulsion-dependent processes via bidirectional signaling through ephrin B transmembrane proteins. Here, we demonstrate that Reelin binds to the extracellular domains of EphB transmembrane proteins, inducing receptor clustering and activation of EphB forward signaling in neurons, independently of the 'classical' Reelin receptors, ApoER2 and VLDLR. Accordingly, mice lacking EphB1 and EphB2 display a positioning defect of CA3 hippocampal pyramidal neurons, similar to that in Reelin-deficient mice, and this cell migration defect depends on the kinase activity of EphB proteins. Together, our data provide biochemical and functional evidence for signal integration between Reelin and EphB forward signaling. |
| Databáze: | OpenAIRE |
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