Integrin β1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior
| Autor: | Shannon L. Gourley, William D. Bradley, Mark A. Simpson, Louis F. Reichardt, Yu-Chih Lin, Michael Sloan Warren, Jane R. Taylor, Anthony J. Koleske, Charles A. Greer |
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| Rok vydání: | 2012 |
| Předmět: |
Male
RHOA Integrin Green Fluorescent Proteins Enzyme-Linked Immunosorbent Assay Nerve Tissue Proteins Hippocampal formation CD49c Hippocampus Article Synapse src Homology Domains Mice Organ Culture Techniques Cocaine Avoidance Learning Basic Helix-Loop-Helix Transcription Factors Animals Immunoprecipitation Cells Cultured Mice Knockout Neurons Analysis of Variance biology General Neuroscience Integrin beta1 GTPase-Activating Proteins Post-Synaptic Density Recognition Psychology Dendrites Repressor Proteins Animals Newborn Mutation Synapses biology.protein Exploratory Behavior Integrin beta 6 alpha-Fetoproteins Signal transduction Postsynaptic density Neuroscience Protein Binding Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(8) |
| ISSN: | 1529-2401 |
| Popis: | Integrins are heterodimeric extracellular matrix receptors that are essential for the proper development of the vertebrate nervous system. We report here that selective loss of integrin β1 in excitatory neurons leads to reductions in the size and complexity of hippocampal dendritic arbors, hippocampal synapse loss, impaired hippocampus-dependent learning, and exaggerated psychomotor sensitivity to cocaine in mice. Our biochemical and genetic experiments demonstrate that the intracellular tail of integrin β1 binds directly to Arg kinase and that this interaction stimulates activity of the Arg substrate p190RhoGAP, an inactivator of the RhoA GTPase. Moreover, genetic manipulations that reduce integrin β1 signaling through Arg recapitulate the integrin β1 knock-out phenotype in a gene dose-sensitive manner. Together, these results describe a novel integrin β1–Arg–p190RhoGAP pathway that regulates dendritic arbor size, promotes synapse maintenance, supports proper hippocampal function, and mitigates the behavioral consequences of cocaine exposure. |
| Databáze: | OpenAIRE |
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