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

Alan Jung Park, Mahesh Shivarama Shetty, Jay M. Baraban, Ted Abel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number145
JournalMolecular Brain
Volume13
Issue number1
DOIs
StatePublished - Dec 2020

Keywords

  • FMRP
  • Hippocampal synaptic plasticity
  • Local protein synthesis
  • Long-term depression
  • Long-term potentiation
  • PKA
  • RNA-binding protein
  • Translin
  • Trax
  • microRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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