E3 ubiquitin ligase Nedd4-2 exerts neuroprotective effects during endoplasmic reticulum stress.

ABSTRACT: The neural precursor cell expressed developmentally down-regulated protein 4-like (Nedd4-2) is an E3 ubiquitin ligase critical for neurodevelopment and homeostasis of neural circuit excitability. While dysregulation of Nedd4-2 has been linked to elevated seizure susceptibility through impaired ubiquitination of multiple direct substrates, it remains largely unclear whether Nedd4-2 interconnects other cellular pathways that affect neuronal activity and seizure susceptibility. Here, we first showed that Nedd4-2 associates with the endoplasmic reticulum (ER) and regulates the expression of multiple ER-resident proteins. Furthermore, utilizing Nedd4-2 conditional knockout mice, we showed that Nedd4-2 is required for the maintenance of spontaneous neural activity and excitatory synapses followi

SUBMITTER: Lodes DE 

PROVIDER: S-EPMC8930443 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature