| http://purl.uniprot.org/citations/31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31046837 | http://www.w3.org/2000/01/rdf-schema#comment | "Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a common feature of Parkinson's disease (PD) and further suggests that several PD-related genes are responsible for ER dysfunction. However, the underlying mechanisms are largely unknown. Here, we defined the mechanism by which LRRK2-G2019S (LRRK2-GS), a pathogenic mutation in the PD-associated gene LRRK2, accelerates ER stress and cell death. Treatment of cells with α-synuclein increased the expression of ER stress proteins and subsequent cell death in LRRK2-GS astrocytes. Intriguingly, we found that LRRK2-GS localizes to the ER membrane, where it interacts with sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and suppress its activity by preventing displacement of phospholamban (PLN). LRRK2-GS-mediated SERCA malfunction leads to ER Ca2+ depletion, which induces the formation of mitochondria-ER contacts and subsequent Ca2+ overload in mitochondria, ultimately resulting in mitochondrial dysfunction. Collectively, our data suggest that, in astrocytes, LRRK2-GS impairs ER Ca2+ homeostasis, which determines cell survival, and as a result, could contribute to the development of PD."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.org/dc/terms/identifier | "doi:10.1186/s40478-019-0716-4"xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/author | "Lee J.H."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/author | "Kim H."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/author | "Park S.M."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/author | "Han J.H."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/author | "Joe E.H."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/author | "Jou I."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/name | "Acta Neuropathol Commun"xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/pages | "68"xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/title | "Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes."xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/31046837 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31046837 |
| http://purl.uniprot.org/citations/31046837 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31046837 |
| http://purl.uniprot.org/uniprot/#_A0A218N881-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_D3YW45-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_D3YXF4-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_D3YXN6-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_P63101-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_A2A5N1-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_A2A5N2-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_A0A2I3BQ03-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |
| http://purl.uniprot.org/uniprot/#_A3KML3-mappedCitation-31046837 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31046837 |