Related Experiment Video

Updated: Feb 11, 2026

3D Modeling of Dendritic Spines with Synaptic Plasticity
07:13

3D Modeling of Dendritic Spines with Synaptic Plasticity

Published on: May 18, 2020

7.4K

NMDAR-dependent Argonaute 2 phosphorylation regulates miRNA activity and dendritic spine plasticity

Dipen Rajgor1, Thomas M Sanderson2, Mascia Amici2

  • 1Centre for Synaptic Plasticity and School of Biochemistry, University of Bristol, Bristol, UK.

The EMBO Journal
|May 2, 2018
PubMed

Insights

NMDA receptor stimulation rapidly represses protein translation via Akt-dependent Ago2 phosphorylation, controlling synaptic plasticity and dendritic spine morphology. This mechanism specifically impacts structural changes, not AMPAR trafficking.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • MicroRNAs (miRNAs) regulate protein expression by forming the RNA-induced silencing complex (RISC) with Argonaute (Ago) proteins.
  • Specific miRNAs are crucial for NMDA receptor (NMDAR)-dependent synaptic plasticity, influencing proteins involved in dendritic spine development and synaptic transmission.

Purpose of the Study:

  • To elucidate the mechanism by which NMDAR stimulation rapidly enhances RISC activity for synaptic protein translation repression.
  • To investigate the role of Ago2 phosphorylation in mediating NMDAR-dependent translational control.

Main Methods:

  • Investigated the effect of NMDAR stimulation on Ago2 phosphorylation at S387.
  • Assessed the interaction between Ago2 and GW182 following NMDAR stimulation.
  • Quantified the translational repression of LIMK1 mediated by miR-134.
  • Examined the requirement of Ago2 S387 phosphorylation for NMDAR-dependent LIMK1 down-regulation and dendritic spine shrinkage.

Main Results:

  • NMDAR stimulation transiently increases Akt-dependent Ago2 phosphorylation at S387.
  • Phospho-Ago2 at S387 enhances binding to GW182, leading to rapid translational repression of LIMK1 via miR-134.
  • NMDAR-dependent reduction of LIMK1 translation and dendritic spine shrinkage require Ago2 S387 phosphorylation.
  • This Ago2 phosphorylation mechanism is specific to structural plasticity and does not affect AMPA receptor trafficking or hippocampal long-term depression (LTD).

Conclusions:

  • A novel mechanism links NMDAR stimulation to miRNA-mediated translational repression through Ago2 phospho-regulation.
  • This pathway rapidly controls dendritic spine morphology by modulating LIMK1 translation.
  • The findings define a specific molecular pathway for NMDAR-dependent structural plasticity.
Keywords:
ArgonauteMicroRNAdendritic spinephosphorylationsynaptic plasticitytranslation

More Related Videos

Analysis of Dendritic Spine Morphology in Cultured CNS Neurons11:48

Analysis of Dendritic Spine Morphology in Cultured CNS Neurons

Published on: July 13, 2011

35.8K
Imaging Dendritic Spines in Caenorhabditis elegans09:14

Imaging Dendritic Spines in Caenorhabditis elegans

Published on: September 27, 2021

2.8K

Related Concept Videos

Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
54.3K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
136.5K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.7K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.6K
Plasticity00:58

Plasticity

Plasticity is the property where an object loses its elasticity and undergoes irreversible deformation, even after the deformation forces are eliminated. If a material deforms irreversibly without increasing stress or load, then this is called ideal plasticity. For example, when a force is applied to an aluminum rod, it changes its shape, but it does not return to its original shape once the force is removed. Plastic deformation or ductility is thus a permanent deformation or change in the...
3.1K