Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons
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 synapti...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719313300 |
| _version_ | 1819020858038943744 |
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| author | Matthew E. Klein Thomas J. Younts Carmen Freire Cobo Adina R. Buxbaum Jonathan Aow Hediye Erdjument-Bromage Stéphane Richard Roberto Malinow Thomas A. Neubert Robert H. Singer Pablo E. Castillo Bryen A. Jordan |
| author_facet | Matthew E. Klein Thomas J. Younts Carmen Freire Cobo Adina R. Buxbaum Jonathan Aow Hediye Erdjument-Bromage Stéphane Richard Roberto Malinow Thomas A. Neubert Robert H. Singer Pablo E. Castillo Bryen A. Jordan |
| author_sort | Matthew E. Klein |
| collection | DOAJ |
| description | 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. : 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. Keywords: RNA-binding proteins, mRNA localization, Arc, Arg3.1, local translation, interactome, isobaric tags, proteomic, RNAscope |
| first_indexed | 2024-12-21T03:57:53Z |
| format | Article |
| id | doaj.art-232f6d1042a2448db13d6265a23fcfc1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T03:57:53Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-232f6d1042a2448db13d6265a23fcfc12022-12-21T19:16:47ZengElsevierCell Reports2211-12472019-11-0129717891799.e6Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal NeuronsMatthew E. Klein0Thomas J. Younts1Carmen Freire Cobo2Adina R. Buxbaum3Jonathan Aow4Hediye Erdjument-Bromage5Stéphane Richard6Roberto Malinow7Thomas A. Neubert8Robert H. Singer9Pablo E. Castillo10Bryen A. Jordan11Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USADominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USADominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USADepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA 92093, USACenter for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA 92093, USADepartment of Cell Biology and Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USASegal Cancer Center, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montréal, QC H3T 1E2, CanadaCenter for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA 92093, USADepartment of Cell Biology and Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USADominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Janelia Research Campus of the Howard Hughes Medical Institute, Ashburn, VA 20147, USADominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USADominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Corresponding authorSummary: 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. : 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. Keywords: RNA-binding proteins, mRNA localization, Arc, Arg3.1, local translation, interactome, isobaric tags, proteomic, RNAscopehttp://www.sciencedirect.com/science/article/pii/S2211124719313300 |
| spellingShingle | Matthew E. Klein Thomas J. Younts Carmen Freire Cobo Adina R. Buxbaum Jonathan Aow Hediye Erdjument-Bromage Stéphane Richard Roberto Malinow Thomas A. Neubert Robert H. Singer Pablo E. Castillo Bryen A. Jordan Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons Cell Reports |
| title | Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons |
| title_full | Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons |
| title_fullStr | Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons |
| title_full_unstemmed | Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons |
| title_short | Sam68 Enables Metabotropic Glutamate Receptor-Dependent LTD in Distal Dendritic Regions of CA1 Hippocampal Neurons |
| title_sort | sam68 enables metabotropic glutamate receptor dependent ltd in distal dendritic regions of ca1 hippocampal neurons |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719313300 |
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