alpha-Synuclein filaments bind the transcriptional regulator HMGB-1.
Abnormal accumulation of alpha-synuclein filaments in Lewy bodies is a neuropathological hallmark of Parkinson's disease and sequestration of cellular protein into these protein aggregates may contribute to the degenerative process. We identified the transcriptional co-factor high mobility group protein 1 (HMGB-1) as a ligand for alpha-synuclein filaments by a filament spin-down technique, mass spectrometric peptide mapping and immunoblotting. HMGB-1 binds preferentially to aggregated alpha-synuclein and is present in alpha-synuclein filament-containing Lewy bodies isolated from brain tissue affected with dementia with Lewy bodies or Parkinson's disease. Our results demonstrate that alpha-synuclein filaments hold the potential for disturbing the cellular gene expression as they can sequester a component involved in cellular transcription regulation.
Lindersson
Evo K
EK
Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark.
Højrup
Peter
P
Gai
Wei Ping
WP
Locker
Daniel
D
Martin
Davy
D
Jensen
Poul Henning
PH
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D024243:HMGB1 Protein / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007456:Iodine Isotopes / Q000378:metabolism; D016631:Lewy Bodies / Q000378:metabolism; D020961:Lewy Body Disease / Q000378:metabolism; D008024:Ligands; D016253:Microscopy, Immunoelectron / Q000379:methods; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism* / Q000648:ultrastructure; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D010449:Peptide Mapping / Q000379:methods; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D024243:HMGB1 Protein; D007456:Iodine Isotopes; D008024:Ligands; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C497604:SNCA protein, human; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein