A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of Na_V1.2 Sodium Channels.

ABSTRACT: Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to Na_V1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of Na_V1.2. Knockout of PTPRN in hippocampal granule cells leads to augmente

SUBMITTER: Wang Y 

PROVIDER: S-EPMC11304301 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature