| http://purl.uniprot.org/citations/34910912 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34910912 | http://www.w3.org/2000/01/rdf-schema#comment | "What percentage of the protein function is required to prevent disease symptoms is a fundamental question in genetic disorders. Decreased transsynaptic LGI1-ADAM22 protein complexes, because of their mutations or autoantibodies, cause epilepsy and amnesia. However, it remains unclear how LGI1-ADAM22 levels are regulated and how much LGI1-ADAM22 function is required. Here, by genetic and structural analysis, we demonstrate that quantitative dual phosphorylation of ADAM22 by protein kinase A (PKA) mediates high-affinity binding of ADAM22 to dimerized 14-3-3. This interaction protects LGI1-ADAM22 from endocytosis-dependent degradation. Accordingly, forskolin-induced PKA activation increases ADAM22 levels. Leveraging a series of ADAM22 and LGI1 hypomorphic mice, we find that ∼50% of LGI1 and ∼10% of ADAM22 levels are sufficient to prevent lethal epilepsy. Furthermore, ADAM22 function is required in excitatory and inhibitory neurons. These results suggest strategies to increase LGI1-ADAM22 complexes over the required levels by targeting PKA or 14-3-3 for epilepsy treatment."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.celrep.2021.110107"xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Goto T."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Miyazaki Y."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Abe M."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Fukai S."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Fukata M."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Fukata Y."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Yokoi N."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Kassai H."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Meijer D."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Yamagata A."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Sakimura K."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Sanbo M."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Hirabayashi M."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/author | "Okatsu K."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/name | "Cell Rep"xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/pages | "110107"xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/title | "14-3-3 proteins stabilize LGI1-ADAM22 levels to regulate seizure thresholds in mice."xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://purl.uniprot.org/core/volume | "37"xsd:string |
| http://purl.uniprot.org/citations/34910912 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34910912 |
| http://purl.uniprot.org/citations/34910912 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34910912 |