EphA4 Signaling Regulates Phospholipase Cγ1 Activation, Cofilin Membrane Association, and Dendritic Spine Morphology
| Autor: | Lei Zhou, Amadou T. Corera, Guy Doucet, David Bouvier, Michael Haber, Keith K. Murai, Andreas H. Zisch, Emma V. Jones, Sarah J. Martinez, Edward A. Fon |
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| Rok vydání: | 2007 |
| Předmět: |
Dendritic spine
Dendritic Spines macromolecular substances Biology Hippocampus Mice Actin remodeling of neurons Organ Culture Techniques Chlorocebus aethiops Animals Phosphorylation Cell Shape Cells Cultured Actin Neuronal Plasticity Phospholipase C gamma General Neuroscience Cell Membrane Receptor EphA4 Articles Cofilin Actin cytoskeleton Protein Structure Tertiary Cell biology Dendritic filopodia Enzyme Activation Actin Cytoskeleton Actin Depolymerizing Factors COS Cells Signal transduction Ephrins Postsynaptic density Signal Transduction Synaptosomes |
| Zdroj: | The Journal of Neuroscience. 27:5127-5138 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1170-07.2007 |
| Popis: | Specialized postsynaptic structures known as dendritic spines are the primary sites of glutamatergic innervation at synapses of the CNS. Previous studies have shown that spines rapidly remodel their actin cytoskeleton to modify their shape and this has been associated with changes in synaptic physiology. However, the receptors and signaling intermediates that restructure the actin network in spines are only beginning to be identified. We reported previously that the EphA4 receptor tyrosine kinase regulates spine morphology. However, the signaling pathways downstream of EphA4 that induce spine retraction on ephrin ligand binding remain poorly understood. Here, we demonstrate that ephrin stimulation of EphA4 leads to the recruitment and activation of phospholipase Cγ1 (PLCγ1) in heterologous cells and in hippocampal slices. This interaction occurs through an Src homology 2 domain of PLCγ1 and requires the EphA4 juxtamembrane tyrosines. In the brain, PLCγ1 is found in multiple compartments of synaptosomes and is readily found in postsynaptic density fractions. Consistent with this, PLC activity is required for the maintenance of spine morphology and ephrin-induced spine retraction. Remarkably, EphA4 and PLC activity modulate the association of the actin depolymerizing/severing factor cofilin with the plasma membrane. Because cofilin has been implicated previously in the structural plasticity of spines, this signaling may enable cofilin to depolymerize actin filaments and restructure spines at sites of ephrin–EphA4 contact. |
| Databáze: | OpenAIRE |
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