title: X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains.
abstract: X11 alpha and X11 beta are two neuronal adaptor proteins that interact with the Alzheimer's disease amyloid precursor protein (APP). X11 alpha and X11 beta stabilise APP and inhibit production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. The mechanisms by which X11 alpha and X11 beta modulate APP processing are not clear but one possibility is that they influence the activity of the secretases that cleave APP to give rise to A beta. Presenilin-1 is required for gamma-secretase activity and here we demonstrate that both X11 alpha and X11 beta interact with presenilin-1. X11/presenilin-1 binding is via two X11 PDZ domains and sequences within the carboxy-terminus of presenilin-1. We also demonstrate that both X11 alpha and X11 beta mediate the formation of complexes between APP and presenilin-1. These results suggest that the X11 regulation of APP processing is controlled, at least in part, via their interactions with APP and presenilin-1.
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, Denmark Hill, London SE5 8AF, United Kingdom.
authors.forename: K F
authors.initials: KF
authors.lastname: Lau
authors.forename: D M
authors.initials: DM
authors.lastname: McLoughlin
authors.forename: C
authors.initials: C
authors.lastname: Standen
authors.forename: C C
authors.initials: CC
authors.lastname: Miller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D053764:Presenilin-1; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human