title: RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils.
abstract: The aggresome is an organelle that recruits aggregated proteins for storage and degradation. We performed an siRNA screen for proteins involved in aggresome formation and identified novel mammalian AAA+ protein disaggregases RuvbL1 and RuvbL2. Depletion of RuvbL1 or RuvbL2 suppressed aggresome formation and caused buildup of multiple cytoplasmic aggregates. Similarly, downregulation of RuvbL orthologs in yeast suppressed the formation of an aggresome-like body and enhanced the aggregate toxicity. In contrast, their overproduction enhanced the resistance to proteotoxic stress independently of chaperone Hsp104. Mammalian RuvbL associated with the aggresome, and the aggresome substrate synphilin-1 interacted directly with the RuvbL1 barrel-like structure near the opening of the central channel. Importantly, polypeptides with unfolded structures and amyloid fibrils stimulated the ATPase activity of RuvbL. Finally, disassembly of protein aggregates was promoted by RuvbL. These data indicate that RuvbL complexes serve as chaperones in protein disaggregation.
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
authors: Nava
authors: N
authors: Zaarur
authors: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, MA, USA.
authors: Xiaobin
authors: X
authors: Xu
authors: INSERM U 1053, University of Bordeaux Segalen, Bordeaux, France.
authors: Patrick
authors: P
authors: Lestienne
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
authors: Anatoli B
authors: AB
authors: Meriin
authors: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, MA, USA.
authors: Mark
authors: M
authors: McComb
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, MA, USA.
authors: Catherine E
authors: CE
authors: Costello
authors: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors: Gary P
authors: GP
authors: Newnam
authors: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors: Rakhee
authors: R
authors: Ganti
authors: Laboratory of Amyloid Biology and Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
authors: Nina V
authors: NV
authors: Romanova
authors: Department of Chemistry, University at Albany, State University of New York, Albany, NY, USA.
authors: Maruda
authors: M
authors: Shanmugasundaram
authors: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Sara T N
authors: ST
authors: Silva
authors: Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.
authors: Tiago M
authors: TM
authors: Bandeiras
authors: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.
authors: Pedro M
authors: PM
authors: Matias
authors: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors: Kirill S
authors: KS
authors: Lobachev
authors: Department of Chemistry, University at Albany, State University of New York, Albany, NY, USA.
authors: Igor K
authors: IK
authors: Lednev
authors: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA Laboratory of Amyloid Biology and Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia yury.chernoff@biology.gatech.edu sherma1@bu.edu.
authors: Yury O
authors: YO
authors: Chernoff
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA yury.chernoff@biology.gatech.edu sherma1@bu.edu.
authors: Michael Y
authors: MY
authors: Sherman
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015388:Organelles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000682:Amyloid; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; C118958:SNCAIP protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human; C122079:RUVBL2 protein, human
keywords: RuvbL; aggresome; amyloid; disaggregation