Neural activity controls the synaptic accumulation of alpha-synuclein

• Published in: The Journal of neuroscience Vol. 25; no. 47; pp. 10913 - 10921
• Main Authors: Fortin, Doris L, Nemani, Venu M, Voglmaier, Susan M, Anthony, Malcolm D, Ryan, Timothy A, Edwards, Robert H
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 23.11.2005
• Subjects: alpha-Synuclein - metabolism; Animals; Cells, Cultured; Exocytosis - physiology; Green Fluorescent Proteins; Hippocampus - cytology; Kinetics; Membrane Fusion - physiology; Nerve Endings - metabolism; Neurobiology of Disease; Neurons - metabolism; Neurons - physiology; Presynaptic Terminals - metabolism; Rats; Synapses - metabolism; Synaptic Vesicles - metabolism; Time Factors
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.2922-05.2005

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.