Reelin signals through apolipoprotein E receptor 2 and Cdc42 to increase growth cone motility and filopodia formation
| Autor: | Frank Henle, Michael Frotscher, Günter Roth, Carsten Schwan, Hans H. Bock, Lutz Hein, Dieter K. Meyer, Jost Leemhuis, Marina Pichler, Joachim Herz, Elisabeth Bouché |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Low-density lipoprotein receptor-related protein 8
Cell Adhesion Molecules Neuronal Growth Cones Nerve Tissue Proteins GTPase CDC42 Biology Article Mice Phosphatidylinositol 3-Kinases Organ Culture Techniques Cell Movement Animals Humans Reelin Pseudopodia Growth cone cdc42 GTP-Binding Protein Cells Cultured LDL-Receptor Related Proteins Receptors Lipoprotein Cerebral Cortex Mice Knockout Extracellular Matrix Proteins General Neuroscience Serine Endopeptidases DAB1 Cell biology Rats Reelin Protein HEK293 Cells Cdc42 GTP-Binding Protein nervous system Animals Newborn biology.protein Signal transduction Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(44) |
| ISSN: | 1529-2401 |
| Popis: | Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an apolipoprotein E receptor 2-, Disabled-1-, and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/PACAP38 system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development. Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders. |
| Databáze: | OpenAIRE |
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