Synucleins regulate the kinetics of synaptic vesicle endocytosis

Karina J. Vargas, Sachin Makani, Taylor Davis, Christopher H. Westphal, Pablo E. Castillo, Sreeganga S. Chandra

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Genetic and pathological studies link α-synuclein to the etiology of Parkinson's disease (PD), but the normal function of this presynaptic protein remains unknown. α-Synuclein, an acidic lipid binding protein, shares high sequence identity with β- and γ-synuclein. Previous studies have implicated synucleins in synaptic vesicle (SV) trafficking, although the precise site of synuclein action continues to be unclear. Here we show, using optical imaging, electron microscopy, and slice electrophysiology, that synucleins are required for the fast kinetics of SV endocytosis. Slowed endocytosis observed in synuclein null cultures can be rescued by individually expressing mouse α-, β-, or γ-synuclein, indicating they are functionally redundant. Through comparisons to dynamin knock-out synapses and biochemical experiments, we suggest that synucleins act at early steps of SV endocytosis. Our results categorize α-synuclein with other familial PD genes known to regulate SV endocytosis, implicating this pathway in PD.

Original languageEnglish (US)
Pages (from-to)9364-9376
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number28
DOIs
StatePublished - Jan 1 2014

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Keywords

  • AP180
  • Endocytosis
  • Membrane bending
  • Parkinson's disease
  • Presynaptic
  • Synaptobrevin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Vargas, K. J., Makani, S., Davis, T., Westphal, C. H., Castillo, P. E., & Chandra, S. S. (2014). Synucleins regulate the kinetics of synaptic vesicle endocytosis. Journal of Neuroscience, 34(28), 9364-9376. https://doi.org/10.1523/JNEUROSCI.4787-13.2014