Abstract
The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK. Overexpression of dominant-negative EphB receptor, catalytically inactive kalirin, or dominant-negative Rac1, or inhibition of PAK eliminates ephrin-induced spine development. This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Blotting, Western
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Carrier Proteins*
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Cells, Cultured
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Dendrites / drug effects*
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Dendrites / ultrastructure
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Guanine Nucleotide Exchange Factors / physiology*
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Hippocampus / cytology
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Hippocampus / embryology*
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Humans
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Indicators and Reagents
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Morphogenesis
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Neuronal Plasticity / physiology
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Phosphorylation
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Receptors, Eph Family / physiology*
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Rho Guanine Nucleotide Exchange Factors
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Signal Transduction / physiology
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Synapses / physiology*
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Synapses / ultrastructure
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Tissue Fixation
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Transfection
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rac1 GTP-Binding Protein / physiology
Substances
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Carrier Proteins
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Guanine Nucleotide Exchange Factors
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Indicators and Reagents
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Kalrn protein, rat
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Rho Guanine Nucleotide Exchange Factors
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Receptors, Eph Family
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rac1 GTP-Binding Protein