The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression.

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Neuronal function and synaptic plasticity rely on controlled mRNA translation in dendrites.
• The exon junction complex (EJC) protein eIF4AIII is involved in mRNA processing and transport.

Purpose of the Study:

• To investigate the role of eIF4AIII in neuronal mRNA granules and dendritic mRNAs.
• To determine the impact of eIF4AIII on synaptic strength, AMPA receptor abundance, and ARC protein levels.

Main Methods:

• Association of eIF4AIII with neuronal mRNA granules and dendritic mRNAs.
• Knockdown of eIF4AIII in neurons.
• Measurement of synaptic strength and GLUR1 AMPA receptor abundance.
• Analysis of ARC protein and arc mRNA levels.
• Computational identification of nonsense-mediated decay (NMD) candidates.

Main Results:

• eIF4AIII is localized to neuronal mRNA granules and dendritic mRNAs.
• eIF4AIII knockdown significantly increases synaptic strength and GLUR1 AMPA receptor abundance.
• Depletion of eIF4AIII elevates ARC protein levels, which is crucial for long-term potentiation.
• arc mRNA, abundant in dendrites, is identified as a target for NMD.
• Novel NMD candidates affecting synaptic activity were computationally discovered.

Conclusions:

• eIF4AIII plays a critical role in regulating protein synthesis at synapses.
• Translation-dependent decay pathways, like NMD, may act as essential regulators of protein synthesis in neurons.
• These findings provide insights into the mechanisms controlling spatially and temporally restricted protein expression in neurons.