Synapsin E-domain is essential for α-synuclein function

Alexandra Stavsky; Leonardo A Parra-Rivas; Shani Tal; Jen Riba; Kayalvizhi Madhivanan; Subhojit Roy; Daniel Gitler

doi:10.1101/2023.06.24.546170

Synapsin E-domain is essential for α-synuclein function

bioRxiv [Preprint]. 2023 Dec 7:2023.06.24.546170. doi: 10.1101/2023.06.24.546170.

Authors

Alexandra Stavsky¹, Leonardo A Parra-Rivas^{2

3}, Shani Tal¹, Jen Riba¹, Kayalvizhi Madhivanan^{2

4}, Subhojit Roy^{2

5

3}, Daniel Gitler¹

Affiliations

¹ Department of Physiology and Cell Biology, Faculty of Health Sciences and School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer Sheva, Israel.
² Department of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
³ Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815.
⁴ Current address: Arrowhead Pharmaceuticals, Pasadena, CA, 91105.
⁵ Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.

Abstract

The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin E-domain allows α-syn functionality, binds to α-syn, and is necessary and sufficient for enabling effects of α-syn at the synapse. Together with previous studies implicating the E-domain in clustering SVs, our experiments advocate a cooperative role for these two proteins in maintaining physiologic SV clusters.

Keywords: pHluorin; synapses; synapsin; vesicle pools; α-synuclein.

Publication types

Preprint

Abstract

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