| http://purl.uniprot.org/citations/27597756 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27597756 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27597756 | http://www.w3.org/2000/01/rdf-schema#comment | "Munc18-1 is a key component of the exocytic machinery that controls neurotransmitter release. Munc18-1 heterozygous mutations cause developmental defects and epileptic phenotypes, including infantile epileptic encephalopathy (EIEE), suggestive of a gain of pathological function. Here, we used single-molecule analysis, gene-edited cells, and neurons to demonstrate that Munc18-1 EIEE-causing mutants form large polymers that coaggregate wild-type Munc18-1 in vitro and in cells. Surprisingly, Munc18-1 EIEE mutants also form Lewy body-like structures that contain α-synuclein (α-Syn). We reveal that Munc18-1 binds α-Syn, and its EIEE mutants coaggregate α-Syn. Likewise, removal of endogenous Munc18-1 increases the aggregative propensity of α-Syn(WT) and that of the Parkinson's disease-causing α-Syn(A30P) mutant, an effect rescued by Munc18-1(WT) expression, indicative of chaperone activity. Coexpression of the α-Syn(A30P) mutant with Munc18-1 reduced the number of α-Syn(A30P) aggregates. Munc18-1 mutations and haploinsufficiency may therefore trigger a pathogenic gain of function through both the corruption of native Munc18-1 and a perturbed chaperone activity for α-Syn leading to aggregation-induced neurodegeneration."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.org/dc/terms/identifier | "doi:10.1083/jcb.201512016"xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.org/dc/terms/identifier | "doi:10.1083/jcb.201512016"xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Goetz J."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Goetz J."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Xia D."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Xia D."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Collins B.M."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Collins B.M."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Meunier F.A."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Meunier F.A."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Parton R.G."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Parton R.G."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Gambin Y."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Gambin Y."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Sierecki E."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Sierecki E."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Giles N."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Giles N."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Tomatis V.M."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Tomatis V.M."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Chai Y.J."xsd:string |
| http://purl.uniprot.org/citations/27597756 | http://purl.uniprot.org/core/author | "Chai Y.J."xsd:string |