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VPS35 depletion does not impair presynaptic structure and function.

Sonia Vazquez-Sanchez1, Sander Bobeldijk1, Marien P Dekker2

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Retromer, a protein complex vital for brain function, is present at the presynaptic terminal. However, this study found retromer is not essential for synaptic vesicle recycling in neurons.

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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.