PT  - JOURNAL ARTICLE
AU  - Doris L. Fortin
AU  - Venu M. Nemani
AU  - Susan M. Voglmaier
AU  - Malcolm D. Anthony
AU  - Timothy A. Ryan
AU  - Robert H. Edwards
TI  - Neural Activity Controls the Synaptic Accumulation of α-Synuclein
AID  - 10.1523/JNEUROSCI.2922-05.2005
DP  - 2005 Nov 23
TA  - The Journal of Neuroscience
PG  - 10913--10921
VI  - 25
IP  - 47
4099  - http://www.jneurosci.org/content/25/47/10913.short
4100  - http://www.jneurosci.org/content/25/47/10913.full
SO  - J. Neurosci.2005 Nov 23; 25
AB  - The presynaptic protein α-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. α-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 α-synuclein in living neurons, we used fluorescence recovery after photobleaching. Despite its enrichment at the synapse, α-synuclein is highly mobile, with rapid exchange between adjacent synapses. In addition, we find that α-synuclein disperses from the nerve terminal in response to neural activity. Dispersion depends on exocytosis, but unlike other synaptic vesicle proteins, α-synuclein dissociates from the synaptic vesicle membrane after fusion. Furthermore, the dispersion of α-synuclein is graded with respect to stimulus intensity. Neural activity thus controls the normal function of α-synuclein at the nerve terminal and may influence its role in PD.