VPS35 depletion does not impair presynaptic structure and function

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• The endosomal system's role in synaptic vesicle recycling is proposed but poorly understood.
• Retromer, a key endosomal recycling complex, is crucial for neuronal function and linked to neurodegenerative diseases.
• VPS35 is the core subunit of the retromer complex.

Purpose of the Study:

• To investigate the role of retromer in presynaptic structure and function.
• To determine if retromer is essential for the synaptic vesicle cycle.

Main Methods:

• VPS35, the core subunit of retromer, was knocked down in primary hippocampal mouse neurons.
• Retromer dysfunction was measured by assessing GluA1 levels at the plasma membrane.
• Presynaptic ultrastructure, synaptic vesicle release, and retrieval were analyzed.

Main Results:

• VPS35 depletion caused retromer dysfunction, indicated by reduced plasma membrane GluA1.
• Retromer was localized to the mammalian presynaptic terminal.
• VPS35 depletion did not affect presynaptic ultrastructure, synaptic vesicle release, or retrieval.

Conclusions:

• Retromer is present at the presynaptic terminal but not essential for the synaptic vesicle cycle.
• The presynaptic localization of VPS35 suggests retromer may sort other presynaptic cargo via endosomes.