title: Prefoldin prevents aggregation of α-synuclein.
abstract: Protein aggregation is observed in various neurodegeneration diseases, including Parkinson's disease (PD). Alpha-synuclein, a causative gene product of familial PD, is a major component of large aggregates (inclusion bodies) in PD. Prefoldin, a molecular chaperone comprised of six subunits, PFD1~6, prevents misfolding of newly synthesized nascent polypeptides and also prevents aggregation of protein such as a pathogenic form of Huntingtin, a causative gene product of Huntington disease. In this study, we first found that aggregation of TagRFP-tagged wild-type α-synuclein and its pathogenic mutants, but not that of GFP-tagged α-synuclein, occurred in transfected Neuro-2a cells. The fluorescence of GFP is weakened under the condition of pH 4.5-5.0, and TagRFP is a stable red fluorescence protein under an acidic condition. Aggregated TagRFP-wild-type α-synuclein and its pathogenic mutants in Neuro-2a cells were ubiquitinated and were colocalized with the prefoldin complex in the lysosome under this condition. Furthermore, knockdown of PFD2 and PFD5 disrupted prefoldin formation in α-synuclein-expressing cells, resulting in accumulation of aggregates of wild-type and pathogenic α-synuclein and in induction of cell death. The levels of aggregation and cell death in pathogenic α-synuclein-transfected cells tended to be higher than those in wild-type α-synuclein-transfected cells. These results suggest that prefoldin works as a protective factor in aggregated α-synuclein-induced cell death.
authors: Mariko
authors: M
authors: Takano
authors: Erika
authors: E
authors: Tashiro
authors: Akira
authors: A
authors: Kitamura
authors: Hiroshi
authors: H
authors: Maita
authors: Sanae M M
authors: SM
authors: Iguchi-Ariga
authors: Masataka
authors: M
authors: Kinjo
authors: Hiroyoshi
authors: H
authors: Ariga
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D025801:Ubiquitin; D051844:alpha-Synuclein; D000097573:Red Fluorescent Protein; C112806:prefoldin