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?-Synuclein promotes dilation of the exocytotic fusion pore.


ABSTRACT: The protein ?-synuclein has a central role in the pathogenesis of Parkinson's disease. Like that of other proteins that accumulate in neurodegenerative disease, however, the function of ?-synuclein remains unknown. Localization to the nerve terminal suggests a role in neurotransmitter release, and overexpression inhibits regulated exocytosis, but previous work has failed to identify a clear physiological defect in mice lacking all three synuclein isoforms. Using adrenal chromaffin cells and neurons, we now find that both overexpressed and endogenous synuclein accelerate the kinetics of individual exocytotic events, promoting cargo discharge and reducing pore closure ('kiss-and-run'). Thus, synuclein exerts dose-dependent effects on dilation of the exocytotic fusion pore. Remarkably, mutations that cause Parkinson's disease abrogate this property of ?-synuclein without impairing its ability to inhibit exocytosis when overexpressed, indicating a selective defect in normal function.

SUBMITTER: Logan T 

PROVIDER: S-EPMC5404982 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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α-Synuclein promotes dilation of the exocytotic fusion pore.

Logan Todd T   Bendor Jacob J   Toupin Chantal C   Thorn Kurt K   Thorn Kurt K   Edwards Robert H RH  

Nature neuroscience 20170313 5


The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease. Like that of other proteins that accumulate in neurodegenerative disease, however, the function of α-synuclein remains unknown. Localization to the nerve terminal suggests a role in neurotransmitter release, and overexpression inhibits regulated exocytosis, but previous work has failed to identify a clear physiological defect in mice lacking all three synuclein isoforms. Using adrenal chromaffin cells and neur  ...[more]

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