The role of E3 ubiquitin ligases in synapse function in the healthy and diseased brain

Ubiquitination is a key posttranslational modification for the controlled protein degradation and proteostasis. The substrate specificity is determined by a family of E3 ubiquitin ligases, which are encoded by more than 600 genes in the mammalian genome. Gain- or loss-of-function of a number of E3 genes results in neurodegeneration or neurodevelopmental disorders, affecting synapse function. This implies that the specific ubiquitination of synaptic substrates are of crucial importance for the normal neuronal network. In this review, we will summarize the history, current topics, and challenges in the field of ubiquitination-dependent regulations of synaptogenesis and synaptic transmission.

Automated summary

Ubiquitination is crucial for the regulation of synaptogenesis and synaptic transmission, with abnormalities in E3 genes leading to neurodegenerative disorders and impairing synapse function.