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J Neurosci. 2005 Nov 23;25(47):10913-21.

Neural activity controls the synaptic accumulation of alpha-synuclein.

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Department of Neurology, Graduate Program in Biomedical Sciences, University of California, San Francisco, California 94143-2140, USA.


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.

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