Localized recruitment and activation of RhoA underlies dendritic spine morphology in a glutamate receptor–dependent manner
| Autor: | Carlos G. Dotti, Vanessa Schubert, Jorge Santos Da Silva |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Dendritic spine
RHOA Pyridines Dendritic Spines Protein Serine-Threonine Kinases Receptors Metabotropic Glutamate Hippocampus Models Biological Receptors N-Methyl-D-Aspartate Article Potassium Chloride Profilins Actin remodeling of neurons Neurotransmitter receptor medicine Animals Receptors AMPA Enzyme Inhibitors Cells Cultured Research Articles 6-Cyano-7-nitroquinoxaline-2 3-dione Neurons rho-Associated Kinases biology Intracellular Signaling Peptides and Proteins Glutamate receptor Membrane Proteins Cell Biology Actin cytoskeleton Amides Actins Rats Cell biology medicine.anatomical_structure Receptors Glutamate Profilin biology.protein Neuron Dizocilpine Maleate Carrier Proteins rhoA GTP-Binding Protein Disks Large Homolog 4 Protein Excitatory Amino Acid Antagonists Subcellular Fractions Synaptosomes |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200506136 |
| Popis: | Actin is the major cytoskeletal source of dendritic spines, which are highly specialized protuberances on the neuronal surface where excitatory synaptic transmission occurs (Harris, K.M., and S.B. Kater. 1994. Annu. Rev. Neurosci. 17:341–371; Yuste, R., and D.W. Tank. 1996. Neuron. 16:701–716). Stimulation of excitatory synapses induces changes in spine shape via localized rearrangements of the actin cytoskeleton (Matus, A. 2000. Science. 290:754–758; Nagerl, U.V., N. Eberhorn, S.B. Cambridge, and T. Bonhoeffer. 2004. Neuron. 44:759–767). However, what remains elusive are the precise molecular mechanisms by which different neurotransmitter receptors forward information to the underlying actin cytoskeleton. We show that in cultured hippocampal neurons as well as in whole brain synaptosomal fractions, RhoA associates with glutamate receptors (GluRs) at the spine plasma membrane. Activation of ionotropic GluRs leads to the detachment of RhoA from these receptors and its recruitment to metabotropic GluRs. Concomitantly, this triggers a local reduction of RhoA activity, which, in turn, inactivates downstream kinase RhoA-specific kinase, resulting in restricted actin instability and dendritic spine collapse. These data provide a direct mechanistic link between neurotransmitter receptor activity and the changes in spine shape that are thought to play a crucial role in synaptic strength. |
| Databáze: | OpenAIRE |
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