RT Journal Article
SR Electronic
T1 BETA- AND GAMMA-SYNUCLEINS MODULATE SYNAPTIC VESICLE-BINDING OF ALPHA-SYNUCLEIN
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.19.390419
DO 10.1101/2020.11.19.390419
A1 Kathryn E. Carnazza
A1 Lauren Komer
A1 André Pineda
A1 Yoonmi Na
A1 Trudy Ramlall
A1 Vladimir L. Buchman
A1 David Eliezer
A1 Manu Sharma
A1 Jacqueline Burré
YR 2020
UL http://biorxiv.org/content/early/2020/11/20/2020.11.19.390419.abstract
AB α-Synuclein (αSyn), β-synuclein (βSyn), and γ-synuclein (γSyn) are abundantly expressed in the vertebrate nervous system. αSyn functions in neurotransmitter release via binding to and clustering synaptic vesicles and chaperoning of SNARE-complex assembly. The functions of βSyn and γSyn are unknown. Functional redundancy of the three synucleins and mutual compensation when one synuclein is deleted have been proposed, but with conflicting evidence. Here, we demonstrate that βSyn and γSyn have a reduced affinity towards membranes compared to αSyn, and that direct interaction of βSyn or γSyn with αSyn results in reduced membrane binding of αSyn. Our data suggest that all three synucleins affect synapse function, but only αSyn mediates the downstream function of vesicle clustering and SNARE-complex assembly, while βSyn and γSyn modulate the activity of αSyn through regulating its binding to synaptic vesicles.Competing Interest StatementThe authors have declared no competing interest.