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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
An author (Jen Riba) was added to the author list due to contributions included in the revision. Figure 4, which shows the effect of alpha-syn and synapsin on the distribution of synaptic vesicles in the presynaptic terminal was added. Figure 1-figure supplement 1 was added to differentiate between an effect of alpha-syn on the exocytosis and endocytosis segments of synaptic vesicle recycling. Figure 3-figure supplement 1 was added, indicating that the synaptic level of transduced synapsin Ia and synapsin Ia:ScrE-domain do not differ. Figure 3-figure supplement 2 was added, showing that expression of a soluble E-domain does not reinstate synaptic attenuation by alpha-syn, illustrating the significance of its localization to the presynaptic terminal. In this context, we also showed that the SV-localized sypHy-E-domain construct enhances alpha-syn localization at the presynaptic terminals. Discussion of the significance of the effects of alpha-syn on exocytosis and endocytosis was enhanced.
