Integrin α3 is required for late postnatal stability of dendrite arbors, dendritic spines and synapses, and mouse behavior
| Autor: | Anthony J. Koleske, Charles A. Greer, Meghan E. Kerrisk |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Dendritic spine Integrin alpha3 Dendritic Spines Integrin Green Fluorescent Proteins Dendrite Mice Transgenic Nerve Tissue Proteins CD49c Hippocampus Models Biological Article Synapse Mice medicine Basic Helix-Loop-Helix Transcription Factors Animals Immunoprecipitation Neurons Analysis of Variance Memory Disorders biology General Neuroscience Lysine Cell Membrane Age Factors Gene Expression Regulation Developmental Membrane Proteins Long-term potentiation Recognition Psychology Dendrites Actin cytoskeleton Cell biology Mice Inbred C57BL medicine.anatomical_structure Animals Newborn Phosphopyruvate Hydratase Forebrain Synapses biology.protein Female alpha-Fetoproteins rhoA GTP-Binding Protein Neuroscience Disks Large Homolog 4 Protein Guanylate Kinases |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(16) |
| ISSN: | 1529-2401 |
| Popis: | Most dendrite branches and a large fraction of dendritic spines in the adult rodent forebrain are stable for extended periods of time. Destabilization of these structures compromises brain function and is a major contributing factor to psychiatric and neurodegenerative diseases. Integrins are a class of transmembrane extracellular matrix receptors that function as αβ heterodimers and activate signaling cascades regulating the actin cytoskeleton. Here we identify integrin α3 as a key mediator of neuronal stability. Dendrites, dendritic spines, and synapses develop normally in mice with selective loss of integrin α3 in excitatory forebrain neurons, reaching their mature sizes and densities through postnatal day 21 (P21). However, by P42, integrin α3 mutant mice exhibit significant reductions in hippocampal dendrite arbor size and complexity, loss of dendritic spine and synapse densities, and impairments in hippocampal-dependent behavior. Furthermore, gene-dosage experiments demonstrate that integrin α3 interacts functionally with the Arg nonreceptor tyrosine kinase to activate p190RhoGAP, which inhibits RhoA GTPase and regulates hippocampal dendrite and synapse stability and mouse behavior. Together, our data support a fundamental role for integrin α3 in regulating dendrite arbor stability, synapse maintenance, and proper hippocampal function. In addition, these results provide a biochemical and structural explanation for the defects in long-term potentiation, learning, and memory reported previously in mice lacking integrin α3. |
| Databáze: | OpenAIRE |
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