| http://purl.uniprot.org/citations/33651714 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33651714 | http://www.w3.org/2000/01/rdf-schema#comment | "The excitability of interneurons requires Nav1.1, the α subunit of the voltage-gated sodium channel. Nav1.1 deficiency and mutations reduce interneuron excitability, a major pathological mechanism for epilepsy syndromes. However, the regulatory mechanisms of Nav1.1 expression remain unclear. Here, we provide evidence that neddylation is critical to Nav1.1 stability. Mutant mice lacking Nae1, an obligatory component of the E1 ligase for neddylation, in parvalbumin-positive interneurons (PVINs) exhibited spontaneous epileptic seizures and premature death. Electrophysiological studies indicate that Nae1 deletion reduced PVIN excitability and GABA release and consequently increased the network excitability of pyramidal neurons (PyNs). Further analysis revealed a reduction in sodium-current density, not a change in channel property, in mutant PVINs and decreased Nav1.1 protein levels. These results suggest that insufficient neddylation in PVINs reduces Nav1.1 stability and thus the excitability of PVINs; the ensuing increased PyN activity causes seizures in mice. Consistently, Nav1.1 was found reduced by proteomic analysis that revealed abnormality in synapses and metabolic pathways. Our findings describe a role of neddylation in maintaining Nav1.1 stability for PVIN excitability and reveal what we believe is a new mechanism in the pathogenesis of epilepsy."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci136956"xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Chen W."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Dong Z."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Li H."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Liu F."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Luo B."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Ren X."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Sun D."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Su H."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Mei L."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Gao N."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Cui W."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/author | "Xiong W.C."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/pages | "136956"xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/title | "Neddylation stabilizes Nav1.1 to maintain interneuron excitability and prevent seizures in murine epilepsy models."xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://purl.uniprot.org/core/volume | "131"xsd:string |
| http://purl.uniprot.org/citations/33651714 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33651714 |