Synapsin E-domain is essential for α-synuclein function

Elife. 2024 May 7:12:RP89687. doi: 10.7554/eLife.89687.

Abstract

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.

Keywords: alpha-synuclein; cell biology; mouse; neuroscience; presynaptic; synapsin; synaptic terminals; synaptic transmission; synaptic vesicles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Hippocampus* / metabolism
  • Humans
  • Mice
  • Neurons* / metabolism
  • Protein Binding
  • Protein Domains
  • Synapses / metabolism
  • Synapsins* / genetics
  • Synapsins* / metabolism
  • Synaptic Vesicles / metabolism
  • alpha-Synuclein* / chemistry
  • alpha-Synuclein* / genetics
  • alpha-Synuclein* / metabolism

Substances

  • alpha-Synuclein
  • Synapsins