TY - JOUR
T1 - Synucleins regulate the kinetics of synaptic vesicle endocytosis
AU - Vargas, Karina J.
AU - Makani, Sachin
AU - Davis, Taylor
AU - Westphal, Christopher H.
AU - Castillo, Pablo E.
AU - Chandra, Sreeganga S.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - AP180
KW - Endocytosis
KW - Membrane bending
KW - Parkinson's disease
KW - Presynaptic
KW - Synaptobrevin
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UR - http://www.scopus.com/inward/citedby.url?scp=84904006504&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4787-13.2014
DO - 10.1523/JNEUROSCI.4787-13.2014
M3 - Article
C2 - 25009269
AN - SCOPUS:84904006504
SN - 0270-6474
VL - 34
SP - 9364
EP - 9376
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 28
ER -