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NMDAR ‐dependent Argonaute 2 phosphorylation regulates mi RNA activity and dendritic spine plasticity
Author(s) -
Rajgor Dipen,
Sanderson Thomas M,
Amici Mascia,
Collingridge Graham L,
Hanley Jonathan G
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797943
Subject(s) - argonaute , microbiology and biotechnology , dendritic spine , synaptic plasticity , gene silencing , translation (biology) , nmda receptor , microrna , biology , phosphorylation , rna , small interfering rna , neuroscience , messenger rna , receptor , hippocampal formation , genetics , gene
Micro RNA s (mi RNA s) repress translation of target mRNA s by associating with Argonaute (Ago) proteins to form the RNA ‐induced silencing complex ( RISC ), underpinning a powerful mechanism for fine‐tuning protein expression. Specific mi RNA s are required for NMDA receptor ( NMDAR )‐dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins. We show that NMDAR stimulation transiently increases Akt‐dependent phosphorylation of Ago2 at S387, which causes an increase in binding to GW 182 and a rapid increase in translational repression of LIMK 1 via miR‐134. Furthermore, NMDAR ‐dependent down‐regulation of endogenous LIMK 1 translation in dendrites and dendritic spine shrinkage requires phospho‐regulation of Ago2 at S387. AMPAR trafficking and hippocampal LTD do not involve S387 phosphorylation, defining this mechanism as a specific pathway for structural plasticity. This work defines a novel mechanism for the rapid transduction of NMDAR stimulation into mi RNA ‐mediated translational repression to control dendritic spine morphology.