α-Synuclein promotes SNARE-complex assembly in vivo and in vitro Academic Article uri icon

Overview

MeSH Major

  • Aging
  • Nerve Degeneration
  • Neurons
  • Presynaptic Terminals
  • SNARE Proteins
  • alpha-Synuclein

abstract

  • Presynaptic nerve terminals release neurotransmitters repeatedly, often at high frequency, and in relative isolation from neuronal cell bodies. Repeated release requires cycles of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-complex assembly and disassembly, with continuous generation of reactive SNARE-protein intermediates. Although many forms of neurodegeneration initiate presynaptically, only few pathogenic mechanisms are known, and the functions of presynaptic proteins linked to neurodegeneration, such as α-synuclein, remain unclear. Here, we show that maintenance of continuous presynaptic SNARE-complex assembly required a nonclassical chaperone activity mediated by synucleins. Specifically, α-synuclein directly bound to the SNARE-protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and promoted SNARE-complex assembly. Moreover, triple-knockout mice lacking synucleins developed age-dependent neurological impairments, exhibited decreased SNARE-complex assembly, and died prematurely. Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging.

publication date

  • September 24, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3235365

Digital Object Identifier (DOI)

  • 10.1126/science.1195227

PubMed ID

  • 20798282

Additional Document Info

start page

  • 1663

end page

  • 7

volume

  • 329

number

  • 5999