Recruitment of the SNX17-Retriever recycling pathway regulates synaptic function and plasticity

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Cell-surface protein trafficking regulates synaptic function.
• SNX27 and SNX17 pathways mediate protein recycling in non-neuronal cells.
• The role of SNX17 in neuronal protein recycling and synaptic function is largely unknown.

Purpose of the Study:

• To investigate the role of the SNX17 pathway in regulating synaptic function and plasticity in cultured hippocampal neurons.
• To elucidate the molecular mechanisms underlying SNX17 recruitment and function at synapses.

Main Methods:

• Primary culture of hippocampal neurons.
• Disruption of the SNX17 pathway.
• Assessment of excitatory synapse number and structure.
• Analysis of structural plasticity during chemical long-term potentiation (cLTP).
• Investigation of molecular interactions and signaling pathways involved in SNX17 recruitment.

Main Results:

• Disruption of the SNX17 pathway leads to a loss of excitatory synapses.
• The SNX17 pathway is essential for structural plasticity during cLTP.
• cLTP induces SNX17 recruitment to synapses, regulating β1-integrin surface expression.
• SNX17 recruitment to synapses depends on NMDAR activation, CaMKII signaling, and binding to Retriever and PI(3)P.

Conclusions:

• The SNX17 pathway plays a critical role in synaptic maintenance and enduring forms of synaptic plasticity.
• Molecular insights into SNX17 regulation at synapses are provided.
• SNX17 is identified as a key regulator of synaptic structure and plasticity.