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
Department of Pathology, University of California, San Diego, La Jolla, United States; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, United States
Shani Tal
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
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
Kayalvizhi Madhivanan
Department of Pathology, University of California, San Diego, La Jolla, United States
Department of Pathology, University of California, San Diego, La Jolla, United States; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, United States; Department of Neurosciences, University of California, San Diego, La Jolla, United States
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
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 synapses of cultured mouse hippocampal neurons. 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.