| http://purl.uniprot.org/citations/24465216 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24465216 | http://www.w3.org/2000/01/rdf-schema#comment | "Unbiased lipidomic approaches have identified impairments in glycerophosphocholine second messenger metabolism in patients with Alzheimer's disease. Specifically, we have shown that amyloid-β42 signals the intraneuronal accumulation of PC(O-16:0/2:0) which is associated with neurotoxicity. Similar to neuronal cells, intracellular accumulation of PC(O-16:0/2:0) is also toxic to Saccharomyces cerevisiae, making yeast an excellent model to decipher the pathological effects of this lipid. We previously reported that phospholipase D, a phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2)-binding protein, was relocalized in response to PC(O-16:0/2:0), suggesting that this neurotoxic lipid may remodel lipid signaling networks. Here we show that PC(O-16:0/2:0) regulates the distribution of the PtdIns(4)P 5-kinase Mss4 and its product PtdIns(4,5)P2 leading to the formation of invaginations at the plasma membrane (PM). We further demonstrate that the effects of PC(O-16:0/2:0) on the distribution of PM PtdIns(4,5)P2 pools are in part mediated by changes in the biosynthesis of long chain bases (LCBs) and ceramides. A combination of genetic, biochemical and cell imaging approaches revealed that PC(O-16:0/2:0) is also a potent inhibitor of signaling through the Target of rampamycin complex 2 (TORC2). Together, these data provide mechanistic insight into how specific disruptions in phosphocholine second messenger metabolism associated with Alzheimer's disease may trigger larger network-wide disruptions in ceramide and phosphoinositide second messenger biosynthesis and signaling which have been previously implicated in disease progression."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1004010"xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Kennedy M.A."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Harris L.J."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Johnston A."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Baetz K."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Abreu S."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Reggiori F."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Dunn T."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Gable K."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Loewith R."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Bennett S.A."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/author | "Niewola-Staszkowska K."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/pages | "e1004010"xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/title | "A neurotoxic glycerophosphocholine impacts PtdIns-4, 5-bisphosphate and TORC2 signaling by altering ceramide biosynthesis in yeast."xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/24465216 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24465216 |
| http://purl.uniprot.org/citations/24465216 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24465216 |
| http://purl.uniprot.org/uniprot/#_P38994-mappedCitation-24465216 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24465216 |
| http://purl.uniprot.org/uniprot/#_P37297-mappedCitation-24465216 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24465216 |
| http://purl.uniprot.org/uniprot/#_P18961-mappedCitation-24465216 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24465216 |
| http://purl.uniprot.org/uniprot/#_P12688-mappedCitation-24465216 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24465216 |