Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects
Diverse molecular mechanisms regulate synaptic composition and function in the mammalian nervous system. The multifunctional protein arginine methyltransferase 8 (PRMT8) possesses both methyltransferase and phospholipase activities. Here we examine the role of this neuron-specific protein in hippoca...
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| Format: | Article |
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Society for Neuroscience
2018
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| Online Access: | http://hdl.handle.net/1721.1/114826 https://orcid.org/0000-0001-5607-113X https://orcid.org/0000-0001-6788-7185 https://orcid.org/0000-0003-1262-0592 |
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| author | Penney, Jay Seo, Jinsoo Kritskiy, Oleg Elmsaouri, Sara Gao, Fan Pao, Ping-Chieh Su, Susan Chih-Chieh Tsai, Li-Huei |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Penney, Jay Seo, Jinsoo Kritskiy, Oleg Elmsaouri, Sara Gao, Fan Pao, Ping-Chieh Su, Susan Chih-Chieh Tsai, Li-Huei |
| author_sort | Penney, Jay |
| collection | MIT |
| description | Diverse molecular mechanisms regulate synaptic composition and function in the mammalian nervous system. The multifunctional protein arginine methyltransferase 8 (PRMT8) possesses both methyltransferase and phospholipase activities. Here we examine the role of this neuron-specific protein in hippocampal plasticity and cognitive function. PRMT8 protein localizes to synaptic sites, and conditional whole-brain Prmt8 deletion results in altered levels of multiple synaptic proteins in the hippocampus, using both male and female mice. Interestingly, these altered protein levels are due to post-transcriptional mechanisms as the corresponding mRNA levels are unaffected. Strikingly, electrophysiological recordings from hippocampal slices of mice lacking PRMT8 reveal multiple defects in excitatory synaptic function and plasticity. Furthermore, behavioral analyses show that PRMT8 conditional knock-out mice exhibit impaired hippocampal-dependent fear learning. Together, these findings establish PRMT8 as an important component of the molecular machinery required for hippocampal neuronal function. |
| first_indexed | 2024-09-23T11:28:06Z |
| format | Article |
| id | mit-1721.1/114826 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:28:06Z |
| publishDate | 2018 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/1148262022-09-27T19:45:17Z Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects Penney, Jay Seo, Jinsoo Kritskiy, Oleg Elmsaouri, Sara Gao, Fan Pao, Ping-Chieh Su, Susan Chih-Chieh Tsai, Li-Huei Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Penney, Jay Seo, Jinsoo Kritskiy, Oleg Elmsaouri, Sara Gao, Fan Pao, Ping-Chieh Su, Susan Chih-Chieh Tsai, Li-Huei Diverse molecular mechanisms regulate synaptic composition and function in the mammalian nervous system. The multifunctional protein arginine methyltransferase 8 (PRMT8) possesses both methyltransferase and phospholipase activities. Here we examine the role of this neuron-specific protein in hippocampal plasticity and cognitive function. PRMT8 protein localizes to synaptic sites, and conditional whole-brain Prmt8 deletion results in altered levels of multiple synaptic proteins in the hippocampus, using both male and female mice. Interestingly, these altered protein levels are due to post-transcriptional mechanisms as the corresponding mRNA levels are unaffected. Strikingly, electrophysiological recordings from hippocampal slices of mice lacking PRMT8 reveal multiple defects in excitatory synaptic function and plasticity. Furthermore, behavioral analyses show that PRMT8 conditional knock-out mice exhibit impaired hippocampal-dependent fear learning. Together, these findings establish PRMT8 as an important component of the molecular machinery required for hippocampal neuronal function. 2018-04-20T19:22:50Z 2018-04-20T19:22:50Z 2017-09 2017-07 2018-04-19T15:25:57Z Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/114826 Penney, Jay et al. “Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects.” The Journal of Neuroscience 37, 36 (August 2017): 8655–8666 © 2017 The Authors https://orcid.org/0000-0001-5607-113X https://orcid.org/0000-0001-6788-7185 https://orcid.org/0000-0003-1262-0592 http://dx.doi.org/10.1523/JNEUROSCI.0591-17.2017 The Journal of Neuroscience Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | Penney, Jay Seo, Jinsoo Kritskiy, Oleg Elmsaouri, Sara Gao, Fan Pao, Ping-Chieh Su, Susan Chih-Chieh Tsai, Li-Huei Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects |
| title | Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects |
| title_full | Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects |
| title_fullStr | Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects |
| title_full_unstemmed | Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects |
| title_short | Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects |
| title_sort | loss of protein arginine methyltransferase 8 alters synapse composition and function resulting in behavioral defects |
| url | http://hdl.handle.net/1721.1/114826 https://orcid.org/0000-0001-5607-113X https://orcid.org/0000-0001-6788-7185 https://orcid.org/0000-0003-1262-0592 |
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