Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

Molecular Brain

Ted Abel¹  Alan Jung Park²  Mahesh Shivarama Shetty³  Jay M. Baraban⁴ 

[1] Department of Biology, University of Pennsylvania, Philadelphia, PA, USA;Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, 2-471 Bowen Science Building, 51 Newton Road, 52242, Iowa City, IA, USA;Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, 2312 Pappajohn Biomedical Discovery Building, 169 Newton Road, 52242, Iowa City, IA, USA;Department of Biology, University of Pennsylvania, Philadelphia, PA, USA;Gogos Lab, Mortimer B. Zuckerman Mind Brain Behavior Institute, Jerome L. Greene Science Center, Columbia University, L5-053, 3227 Broadway, 10027, New York, NY, USA;Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, 2-471 Bowen Science Building, 51 Newton Road, 52242, Iowa City, IA, USA;Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, 2312 Pappajohn Biomedical Discovery Building, 169 Newton Road, 52242, Iowa City, IA, USA;The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA;

关键词: Translin;    Trax;    Long-term potentiation;    Long-term depression;    Local protein synthesis;    Hippocampal synaptic plasticity;    FMRP;    RNA-binding protein;    microRNA;    PKA;   

DOI  :  10.1186/s13041-020-00691-5

来源: Springer

【 摘 要 】

Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. On the contrary, translin KO mice exhibited deficits in N-methyl-d-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.

【 授权许可】

CC BY