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.
Fortin
Doris L
DL
Department of Neurology, Graduate Program in Biomedical Sciences, University of California, San Francisco, California 94143-2140, USA.
Nemani
Venu M
VM
Voglmaier
Susan M
SM
Anthony
Malcolm D
MD
Ryan
Timothy A
TA
Edwards
Robert H
RH
D000818:Animals; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D007700:Kinetics; D008561:Membrane Fusion / Q000502:physiology; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D013997:Time Factors; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein; D049452:Green Fluorescent Proteins