First Author | Vargas KJ | Year | 2014 |
Journal | J Neurosci | Volume | 34 |
Issue | 28 | Pages | 9364-76 |
PubMed ID | 25009269 | Mgi Jnum | J:215304 |
Mgi Id | MGI:5605098 | Doi | 10.1523/JNEUROSCI.4787-13.2014 |
Citation | Vargas KJ, et al. (2014) Synucleins regulate the kinetics of synaptic vesicle endocytosis. J Neurosci 34(28):9364-76 |
abstractText | Genetic and pathological studies link alpha-synuclein to the etiology of Parkinson's disease (PD), but the normal function of this presynaptic protein remains unknown. alpha-Synuclein, an acidic lipid binding protein, shares high sequence identity with beta- and gamma-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 alpha-, beta-, or gamma-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 alpha-synuclein with other familial PD genes known to regulate SV endocytosis, implicating this pathway in PD. |