Role of the E3 ubiquitin ligase dorfin in the degradation of PSD-95 family proteins

Abstract

The post synaptic density (PSD) is a postsynaptic membrane specialization at neuronal synapses. The PSD undergoes dynamic structural changes and protein turnover during synaptic maturation and plasticity. A key mechanism controlling protein turnover is the ubiquitin-proteasome pathway. Here I identified Dorfin, a RING finger-type E3 ubiquitin ligase, as a binding partner of PSD-95, an abundant PSD component that is important for synaptic structure and plasticity. The C terminus of Dorfin interacts with the PDZ domains of PSD-95. Dorfin selectively binds to the PSD-95 family proteins as shown in yeast two-hybrid, coimmunoprecipitation and coclustering assays. Dorfin selectively ubiquitinates PSD-95 and other PSD-95 family proteins. These results suggest that Dorfin, through the degradation of PSD-95 family proteins, contributes to the structural and functional plasticity of synapses.