Functional cooperation of α-synuclein and VAMP2 in synaptic vesicle recycling

Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11113-11115. doi: 10.1073/pnas.1903049116. Epub 2019 May 20.

Abstract

The function of α-synuclein (α-syn) has been long debated, and two seemingly divergent views have emerged. In one, α-syn binds to VAMP2, acting as a SNARE chaperone-but with no effect on neurotransmission-while another posits that α-syn attenuates neurotransmitter release by restricting synaptic vesicle mobilization and recycling. Here, we show that α-syn-VAMP2 interactions are necessary for α-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function.

Keywords: Parkinson’s disease; alpha synuclein; synaptic transmission.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport / physiology
  • Humans
  • Neurons / metabolism
  • SNARE Proteins / metabolism
  • Synaptic Transmission / immunology
  • Synaptic Vesicles / metabolism*
  • Vesicle-Associated Membrane Protein 2 / metabolism*
  • alpha-Synuclein / metabolism*

Substances

  • SNARE Proteins
  • SNCA protein, human
  • VAMP2 protein, human
  • Vesicle-Associated Membrane Protein 2
  • alpha-Synuclein