Back to Search
Start Over
A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of Na V 1.2 Sodium Channels.
- Source :
-
Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Aug; Vol. 11 (29), pp. e2400560. Date of Electronic Publication: 2024 Jun 14. - Publication Year :
- 2024
-
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 <subscript>V</subscript> 1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of Na <subscript>V</subscript> 1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented Na <subscript>V</subscript> 1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage-gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of Na <subscript>V</subscript> 1.2 channels' function.<br /> (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 2198-3844
- Volume :
- 11
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 38874331
- Full Text :
- https://doi.org/10.1002/advs.202400560