PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity.

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Enduring synaptic plasticity, like long-term potentiation (LTP), relies on protein recycling pathways.
• The recruitment mechanisms of these pathways during plasticity remain unclear.
• Phosphatidylinositol-3-phosphate (PI(3)P) regulates endosomal trafficking and is implicated in neurodegeneration.

Purpose of the Study:

• To investigate the role of PI(3)P synthesis in recruiting protein recycling pathways during synaptic plasticity.
• To elucidate the function of SNX17-Retriever and SNX27-Retromer pathways in synaptic plasticity.

Main Methods:

• Primary hippocampal neuron cultures and hippocampal slices.
• Chemical induction of long-term potentiation (cLTP).
• Analysis of PI(3)P synthesis, protein recruitment to endosomes and synapses, and dendritic spine morphology.

Main Results:

• Dynamic PI(3)P synthesis occurs during cLTP.
• PI(3)P synthesis drives the recruitment of SNX17-Retriever and SNX27-Retromer pathways to synapses.
• Both pathways are crucial for cLTP-induced dendritic spine enlargement and parallel cargo recycling.
• Inhibition of PI(3)P synthesis blocks SNX17/SNX27 recruitment, cargo recycling, and LTP.

Conclusions:

• Dynamic PI(3)P synthesis is a key regulator of endocytic recycling at synapses.
• PI(3)P signaling coordinates the recruitment and function of SNX17-Retriever and SNX27-Retromer pathways.
• This mechanism is essential for synaptic plasticity and long-term potentiation.