Format

Send to

Choose Destination
Nat Neurosci. 2017 May;20(5):681-689. doi: 10.1038/nn.4529. Epub 2017 Mar 13.

α-Synuclein promotes dilation of the exocytotic fusion pore.

Author information

1
Departments of Neurology and Physiology, UCSF School of Medicine, University of California, San Francisco, San Francisco, California, USA.
2
Graduate Program in Biomedical Sciences, UCSF School of Medicine, University of California, San Francisco, San Francisco, California, USA.
3
Department of Biochemistry &Biophysics, UCSF School of Medicine, University of California, San Francisco, San Francisco, California, USA.

Abstract

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 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 α-synuclein without impairing its ability to inhibit exocytosis when overexpressed, indicating a selective defect in normal function.

PMID:
28288128
PMCID:
PMC5404982
DOI:
10.1038/nn.4529
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center