RESUMEN
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.
Asunto(s)
Hipocampo , Neuronas , Sinapsinas , alfa-Sinucleína , Animales , Humanos , Ratones , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/química , Células Cultivadas , Hipocampo/metabolismo , Neuronas/metabolismo , Unión Proteica , Dominios Proteicos , Sinapsis/metabolismo , Sinapsinas/metabolismo , Sinapsinas/genética , Vesículas Sinápticas/metabolismoRESUMEN
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.