학술논문

Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects.
Document Type
Article
Source
Journal of Neuroscience. 9/6/2017, Vol. 37 Issue 36, p8655-8666. 12p.
Subject
*PROTEIN arginine methyltransferases
*SYNAPSES
*COGNITIVE ability
*HIPPOCAMPUS (Brain)
*NEUROPLASTICITY
*NEURAL transmission
Language
ISSN
0270-6474
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 PrmtS 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. [ABSTRACT FROM AUTHOR]