Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 47, Pages 10913-10921Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2922-05.2005
Keywords
alpha-synuclein; membrane association; synaptic vesicle; neural activity; Parkinson's disease; synapsin
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Funding
- NINDS NIH HHS [R01 NS036942] Funding Source: Medline
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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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