Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects
Name
Tsai_Loss of protein.pdf
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2.92 MB
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Author(s)
Penney, Jay
Seo, Jinsoo
Kritskiy, Oleg
Elmsaouri, Sara
Gao, Fan
Pao, Ping-Chieh
Su, Susan Chih-Chieh
Tsai, Li-Huei
Date Issued
September 2017
Journal
The Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
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
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1523/JNEUROSCI.0591-17.2017
