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 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.
Subject(s)
Hippocampus , Neurons , Synapsins , alpha-Synuclein , Animals , Humans , Mice , alpha-Synuclein/metabolism , alpha-Synuclein/genetics , alpha-Synuclein/chemistry , Cells, Cultured , Hippocampus/metabolism , Neurons/metabolism , Protein Binding , Protein Domains , Synapses/metabolism , Synapsins/metabolism , Synapsins/genetics , Synaptic Vesicles/metabolismABSTRACT
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.
