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Prefoldin Protects Neuronal Cells from Polyglutamine Toxicity by Preventing Aggregation Formation

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Title: Prefoldin Protects Neuronal Cells from Polyglutamine Toxicity by Preventing Aggregation Formation
Authors: Tashiro, Erika Browse this author
Zako, Tamotsu Browse this author
Muto, Hideki Browse this author
Itoo, Yoshinori Browse this author
Soergjerd, Karin Browse this author
Terada, Naofumi Browse this author
Abe, Akira Browse this author
Miyazawa, Makoto Browse this author
Kitamura, Akira Browse this author
Kitaura, Hirotake Browse this author
Kubota, Hiroshi Browse this author
Maeda, Mizuo Browse this author
Momoi, Takashi Browse this author
Iguchi-Ariga, Sanae M. M. Browse this author →KAKEN DB
Kinjo, Masataka Browse this author →KAKEN DB
Ariga, Hiroyoshi Browse this author →KAKEN DB
Issue Date: 5-Jul-2013
Publisher: American Society for Biochemistry Molecular Biology Inc
Journal Title: Journal of Biological Chemistry
Volume: 288
Issue: 27
Start Page: 19958
End Page: 19972
Publisher DOI: 10.1074/jbc.M113.477984
Abstract: Huntington disease is caused by cell death after the expansion of polyglutamine (polyQ) tracts longer than similar to 40 repeats encoded by exon 1 of the huntingtin (HTT) gene. Prefoldin is a molecular chaperone composed of six subunits, PFD1-6, and prevents misfolding of newly synthesized nascent polypeptides. In this study, we found that knockdown of PFD2 and PFD5 disrupted prefoldin formation in HTT-expressing cells, resulting in accumulation of aggregates of a pathogenic form of HTT and in induction of cell death. Dead cells, however, did not contain inclusions of HTT, and analysis by a fluorescence correlation spectroscopy indicated that knockdown of PFD2 and PFD5 also increased the size of soluble oligomers of pathogenic HTT in cells. In vitro single molecule observation demonstrated that prefoldin suppressed HTT aggregation at the small oligomer (dimer to tetramer) stage. These results indicate that prefoldin inhibits elongation of large oligomers of pathogenic Htt, thereby inhibiting subsequent inclusion formation, and suggest that soluble oligomers of polyQ-expanded HTT are more toxic than are inclusion to cells.
Rights: This research was originally published in Journal of Biological Chemistry. Tashiro, Erika; Zako, Tamotsu; Muto, Hideki; Itoo,Yoshinori; Soergjerd, Karin; Terada, Naofumi;Abe, Akira; Miyazawa, Makoto; Kitamura, Akira; Kitaura, Hirotake; Kubota, Hiroshi; Maeda,Mizuo; Momoi, Takashi; Iguchi-Ariga, Sanae M. M.; Kinjo, Masataka; Ariga, Hiroyoshi;.Prefoldin Protects Neuronal Cells from Polyglutamine Toxicity by Preventing Aggregation Formation. Journal of Biological Chemistry. 2013; 288 (27):pp19958-19972 . © the American Society for Biochemistry and Molecular Biology.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 有賀 寛芳

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