Journal
JOURNAL OF NEUROSCIENCE
Volume 32, Issue 30, Pages 10129-10135Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0535-12.2012
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Funding
- Larry Hillblom Foundation
- Alzheimer's Association [NIRG-08-90769]
- American Federation for Aging Research (AFAR)
- NIH [P50AG005131, R01NS075233]
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Although the presynaptic protein alpha-synuclein is a recognized player in neurodegeneration, its precise physiologic function(s) and/or role in human disease remains unclear. An emerging consensus from previous studies in lower-order systems is that alpha-synuclein interferes with vesicle-trafficking pathways; however putative neuronal correlates are unknown. Here we explore consequences of alpha-synuclein modulation in cultured mouse hippocampal neurons; coupling alpha-synuclein overexpression and knock-out model-systems with contemporary imaging paradigms. Our studies reveal an unexpected role of alpha-synuclein in attenuating the mobility of recycling pool (RP) vesicles between presynaptic boutons-called superpool trafficking-and also in maintaining the overall size of RPs at synapses. While an excess of alpha-synuclein led to smaller RPs and inhibited intersynaptic trafficking, an absence of alpha-synuclein triggered converse changes with larger RPs and enhanced intersynaptic trafficking. The data collectively suggest a model where alpha-synuclein maintains RP homeostasis by modulating intersynaptic vesicular dynamics, and provide a putative neuronal correlate of alpha-synuclein-induced impairments in vesicle-trafficking previously reported in lower-order systems.
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