Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons
| Autor: | Thomas A. Neubert, Carmen Freire Cobo, Jonathan Aow, Bryen A. Jordan, Thomas J. Younts, Hediye Erdjument-Bromage, Adina R. Buxbaum, Pablo E. Castillo, Matthew E. Klein, Stéphane Richard, Robert H. Singer, Roberto Malinow |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
RNA-binding protein Biology Hippocampal formation Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Gene expression Animals lcsh:QH301-705.5 CA1 Region Hippocampal Adaptor Proteins Signal Transducing Mice Knockout Arc (protein) Long-Term Synaptic Depression Pyramidal Cells RNA-Binding Proteins Translation (biology) Dendrites 030104 developmental biology Metabotropic receptor lcsh:Biology (General) Metabotropic glutamate receptor Protein Biosynthesis Synaptic plasticity Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell reports Cell Reports, Vol 29, Iss 7, Pp 1789-1799.e6 (2019) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY The transport and translation of dendritic mRNAs by RNA-binding proteins (RBPs) allows for spatially restricted gene expression in neuronal processes. Although local translation in neuronal dendrites is now well documented, there is little evidence for corresponding effects on local synaptic function. Here, we report that the RBP Sam68 promotes the localization and translation of Arc mRNA preferentially in distal dendrites of rodent hippocampal CA1 pyramidal neurons. Consistent with Arc function in translation-dependent synaptic plasticity, we find that Sam68 knockout (KO) mice display impaired metabotropic glutamate-receptor-dependent long-term depression (mGluR-LTD) and impaired structural plasticity exclusively at distal Schaffer-collateral synapses. Moreover, by using quantitative proteomics, we find that the Sam68 interactome contains numerous regulators of mRNA translation and synaptic function. This work identifies an important player in Arc expression, provides a general framework for Sam68 regulation of protein synthesis, and uncovers a mechanism that enables the precise spatiotemporal expression of long-term plasticity throughout neurons. In Brief Although local translation in neuronal dendrites is well documented, there is little evidence for corresponding effects on local synaptic function. Klein et al. demonstrate that Sam68 is required for Arc protein synthesis at distal dendritic regions and is required for synaptic plasticity exclusively at distal dendrites of hippocampal pyramidal neurons. Graphical Abstract |
| Databáze: | OpenAIRE |
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