Neural activity controls the synaptic accumulation of alpha-synuclein. Academic Article uri icon

Overview

abstract

  • The presynaptic protein alpha-synuclein has a central role in Parkinson's disease (PD). However, the mechanism by which the protein contributes to neurodegeneration and its normal function remain unknown. Alpha-synuclein localizes to the nerve terminal and interacts with artificial membranes in vitro but binds weakly to native brain membranes. To characterize the membrane association of alpha-synuclein in living neurons, we used fluorescence recovery after photobleaching. Despite its enrichment at the synapse, alpha-synuclein is highly mobile, with rapid exchange between adjacent synapses. In addition, we find that alpha-synuclein disperses from the nerve terminal in response to neural activity. Dispersion depends on exocytosis, but unlike other synaptic vesicle proteins, alpha-synuclein dissociates from the synaptic vesicle membrane after fusion. Furthermore, the dispersion of alpha-synuclein is graded with respect to stimulus intensity. Neural activity thus controls the normal function of alpha-synuclein at the nerve terminal and may influence its role in PD.

publication date

  • November 23, 2005

Research

keywords

  • Neurons
  • Synapses
  • alpha-Synuclein

Identity

PubMed Central ID

  • PMC6725870

Scopus Document Identifier

  • 28044461467

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.2922-05.2005

PubMed ID

  • 16306404

Additional Document Info

volume

  • 25

issue

  • 47