Despite considerable evidence linking alpha-synuclein with membranes in vitro, it has proven difficult to demonstrate membrane association of the protein in vivo. alpha-Synuclein localizes to the nerve terminal, but biochemical experiments have not revealed a tight association with membranes. To address the dynamics of the protein in live cells, we have used photobleaching and found that alpha-synuclein exhibits high mobility, although distinctly less than an entirely soluble protein. Further, neural activity controls the distribution of alpha-synuclein, causing its dispersion from the synapse. In addition to the presumed role of alpha-synuclein dynamics in synaptic function, changes in its physiological behavior may underlie the pathological changes associated with Parkinson's disease.
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