Neural activity controls the synaptic accumulation of alpha-synuclein.

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.
Mesh Terms:
Animals, Cells, Cultured, Exocytosis, Green Fluorescent Proteins, Hippocampus, Kinetics, Membrane Fusion, Nerve Endings, Neurons, Presynaptic Terminals, Rats, Synapses, Synaptic Vesicles, Time Factors, alpha-Synuclein
J. Neurosci.
Date: Nov. 23, 2005
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