eLife (May 2024)

Synapsin E-domain is essential for α-synuclein function

  • Alexandra Stavsky,
  • Leonardo A Parra-Rivas,
  • Shani Tal,
  • Jen Riba,
  • Kayalvizhi Madhivanan,
  • Subhojit Roy,
  • Daniel Gitler

DOI
https://doi.org/10.7554/eLife.89687
Journal volume & issue
Vol. 12

Abstract

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The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here, we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin E-domain allows α-syn functionality, binds to α-syn, and is necessary and sufficient for enabling effects of α-syn at synapses of cultured mouse hippocampal neurons. Together with previous studies implicating the E-domain in clustering SVs, our experiments advocate a cooperative role for these two proteins in maintaining physiologic SV clusters.

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