title: The effects of the cellular and infectious prion protein on the neuronal adaptor protein X11α.
abstract: BACKGROUND
  The neuronal adaptor protein X11α is a multidomain protein with a phosphotyrosine binding (PTB) domain, two PDZ (PSD_95, Drosophila disks-large, ZO-1) domains, a Munc Interacting (MI) domain and a CASK interacting region. Amongst its functions is a role in the regulation of the abnormal processing of the amyloid precursor protein (APP). It also regulates the activity of Cu/Zn Superoxide dismutase (SOD1) through binding with its chaperone the copper chaperone for SOD1. How X11α production is controlled has remained unclear.
  
  
  METHODS
  Using the neuroblastoma cell line, N2a, and knockdown studies, the effect of the cellular and infectious prion protein, PrP(C) and PrP(Sc), on X11α is examined.
  
  
  RESULTS
  We show that X11α expression is directly proportional to the expression of PrP(C), whereas its levels are reduced by PrP(Sc). We also show PrP(Sc) to affect X11α at a functional level. One of the effects of prion infection is lowered cellular SOD1 levels, here by knockdown of X11α we identify that the effect of PrP(Sc) on SOD1 can be reversed indicating that X11α is involved in prion disease pathogenesis.
  
  
  CONCLUSIONS
  A role for the cellular and infectious prion protein, PrP(C) and PrP(Sc), respectively, in regulating X11α is identified in this work.
  
  
  CONCLUSIONS
  Due to the multiple interacting partners of X11α, dysfunction or alteration in X11α will have a significant cellular effect. This work highlights the role of PrP(C) and PrP(Sc) in the regulation of X11α, and provides a new target pathway to control X11α and its related functions.
authors: UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Jack
authors: J
authors: O'Sullivan
authors: UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Emma
authors: E
authors: Comerford
authors: UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Walid
authors: W
authors: Rachidi
authors: UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Michael
authors: M
authors: Scott
authors: Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors: Nigel M
authors: NM
authors: Hooper
authors: UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: hilary.mcmahon@ucd.ie.
authors: Hilary E M
authors: HE
authors: McMahon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011328:Prions / Q000502:physiology*; D013482:Superoxide Dismutase / Q000502:physiology; D000072105:Superoxide Dismutase-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513072:Apba1 protein, mouse; D009419:Nerve Tissue Proteins; D011328:Prions; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Neuronal adaptor protein; Prion; Scrapie; Superoxide dismutase