Myosin IIb activity and phosphorylation status determines dendritic spine and post-synaptic density morphology
| Autor: | Hannelore Asmussen, Miguel Vicente-Manzanares, Karen Newell-Litwa, Jennifer L. Hodges, Alan Rick Horwitz |
|---|---|
| Přispěvatelé: | UAM. Departamento de Medicina |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Dendritic spine
Medicina Dendritic Spines lcsh:Medicine macromolecular substances Neurotransmission Biology Receptors N-Methyl-D-Aspartate 03 medical and health sciences Learning and Memory 0302 clinical medicine Developmental Neuroscience Molecular Cell Biology Myosin Animals Pseudopodia Phosphorylation lcsh:Science Rho-associated protein kinase Cytoskeleton Actin 030304 developmental biology 0303 health sciences Nonmuscle Myosin Type IIB Multidisciplinary Neuronal Morphology lcsh:R Post-Synaptic Density musculoskeletal system Cellular Structures Rats Cell biology nervous system Cellular Neuroscience Excitatory postsynaptic potential lcsh:Q Cell Surface Extensions Postsynaptic density 030217 neurology & neurosurgery Research Article Neuroscience Synaptic Plasticity |
| Zdroj: | PLoS ONE, Vol 6, Iss 8, p e24149 (2011) PLoS ONE Biblos-e Archivo. Repositorio Institucional de la UAM instname |
| ISSN: | 1932-6203 |
| Popis: | Dendritic spines in hippocampal neurons mature from a filopodia-like precursor into a mushroom-shape with an enlarged post-synaptic density (PSD) and serve as the primary post-synaptic location of the excitatory neurotransmission that underlies learning and memory. Using myosin II regulatory mutants, inhibitors, and knockdowns, we show that non-muscle myosin IIB (MIIB) activity determines where spines form and whether they persist as filopodia-like spine precursors or mature into a mushroom-shape. MIIB also determines PSD size, morphology, and placement in the spine. Local inactivation of MIIB leads to the formation of filopodia-like spine protrusions from the dendritic shaft. However, di-phosphorylation of the regulatory light chain on residues Thr18 and Ser19 by Rho kinase is required for spine maturation. Inhibition of MIIB activity or a mono-phosphomimetic mutant of RLC similarly prevented maturation even in the presence of NMDA receptor activation. Expression of an actin cross-linking, non-contractile mutant, MIIB R709C, showed that maturation into a mushroom-shape requires contractile activity. Loss of MIIB also leads to an elongated PSD morphology that is no longer restricted to the spine tip; whereas increased MIIB activity, specifically through RLC-T18, S19 di-phosphorylation, increases PSD area. These observations support a model whereby myosin II inactivation forms filopodia-like protrusions that only mature once NMDA receptor activation increases RLC di-phosphorylation to stimulate MIIB contractility, resulting in mushroom-shaped spines with an enlarged PSD This work was supported by National Institutes of Health (NIH) grant (GM23244) and by the Cell and Molecular Biology Training Grant from the NIH (T32-GM008136) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|