DOI: 10.1101/517524Jan 10, 2019Paper

Hsc70 Ameliorates the Vesicle Recycling Defects Caused by Excess &#945-Synuclein at Synapses

BioRxiv : the Preprint Server for Biology
Susan M.L. BanksJennifer R Morgan


Alpha-Synuclein overexpression and aggregation are linked to Parkinsons disease (PD), dementia with Lewy bodies (DLB), and several other neurodegenerative disorders. In addition to effects in the cell body, alpha-synuclein accumulation occurs at presynapses where the protein is normally localized. While it is generally agreed that excess alpha-synuclein impairs synaptic vesicle trafficking, the underlying mechanisms are unknown. We show here that acute introduction of excess human alpha-synuclein at a classic vertebrate synapse, the lamprey reticulospinal synapse, selectively impaired the uncoating of clathrin-coated vesicles (CCVs) during synaptic vesicle recycling, leading to a severe depletion of synaptic vesicles. Furthermore, human alpha-synuclein and lamprey alpha-synuclein both interact in vitro with Hsc70, the chaperone protein that uncoats CCVs at synapses. After introducing excess alpha-synuclein to lamprey axons, Hsc70 availability was reduced at the synapses, suggesting Hsc70 sequestration as a possible mechanism underlying the synaptic vesicle trafficking defects. In support of this hypothesis, increasing the levels of exogenous Hsc70 together with alpha-synuclein ameliorated the CCV uncoating and vesicle recycling...Continue Reading

Related Concepts

Parkinson Disease
Synaptic Vesicles
Lewy Bodies
Molecular Chaperones

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