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BETA- AND GAMMA-SYNUCLEINS MODULATE SYNAPTIC VESICLE-BINDING OF ALPHA-SYNUCLEIN

Kathryn E. Carnazza, View ORCID ProfileLauren Komer, André Pineda, Yoonmi Na, Trudy Ramlall, View ORCID ProfileVladimir L. Buchman, View ORCID ProfileDavid Eliezer, View ORCID ProfileManu Sharma, View ORCID ProfileJacqueline Burré
doi: https://doi.org/10.1101/2020.11.19.390419
Kathryn E. Carnazza
1Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021, USA
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Lauren Komer
1Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021, USA
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  • ORCID record for Lauren Komer
André Pineda
1Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021, USA
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Yoonmi Na
1Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021, USA
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Trudy Ramlall
2Department of Biochemistry, Weill Cornell Medicine, New York, New York 10021, USA
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Vladimir L. Buchman
3School of Biosciences, Cardiff University, Cardiff CF103AX, UK & Institute of Physiologically Active Compounds Russian Academy of Sciences (IPAC RAS), Chernogolovka 142432, Moscow Region, Russian Federation
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David Eliezer
2Department of Biochemistry, Weill Cornell Medicine, New York, New York 10021, USA
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  • ORCID record for David Eliezer
Manu Sharma
1Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021, USA
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Jacqueline Burré
1Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021, USA
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  • For correspondence: jab2058@med.cornell.edu
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SUMMARY

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 20, 2020.
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BETA- AND GAMMA-SYNUCLEINS MODULATE SYNAPTIC VESICLE-BINDING OF ALPHA-SYNUCLEIN
Kathryn E. Carnazza, Lauren Komer, André Pineda, Yoonmi Na, Trudy Ramlall, Vladimir L. Buchman, David Eliezer, Manu Sharma, Jacqueline Burré
bioRxiv 2020.11.19.390419; doi: https://doi.org/10.1101/2020.11.19.390419
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BETA- AND GAMMA-SYNUCLEINS MODULATE SYNAPTIC VESICLE-BINDING OF ALPHA-SYNUCLEIN
Kathryn E. Carnazza, Lauren Komer, André Pineda, Yoonmi Na, Trudy Ramlall, Vladimir L. Buchman, David Eliezer, Manu Sharma, Jacqueline Burré
bioRxiv 2020.11.19.390419; doi: https://doi.org/10.1101/2020.11.19.390419

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