PTPRN mediates endocytosis of NaV1.2 sodium chan-nels and suppresses epileptogenesis in mice
10.3867/j.issn.1000-3002.2023.07.001
- Author:
Yifan WANG
1
,
2
;
Hui YANG
;
Na LI
;
Weining MA
;
Shiqi LIU
;
Hedan CHEN
;
Huifang SONG
;
Xinyue MA
;
Jingyun YI
;
Jingjing LIAN
;
Xinyu TU
;
Chao PENG
;
Zhuo HUANG
Author Information
1. State Key Laboratory of Natural and Biomimetic Drugs,Department of Molecular and Cellular Pharmacology,School of Pharmaceutial Sciences,Peking University,Beijing 100191,China
2. IDG/McGovern Institute for Brain Research,Peking University,Beijing 100871,China
- Keywords:
epilepsy;
PTPRN;
NaV1.2;
NEDD4L;
neuron excitability
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(7):481-481
- CountryChina
- Language:Chinese
-
Abstract:
Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.
