title: NMDA receptor/amyloid precursor protein interactions: a comparison between wild-type and amyloid precursor protein mutations associated with familial Alzheimer's disease.
abstract: Two recent reports showed that amyloid precursor protein (APP) may contribute to postsynaptic mechanisms via the regulation of the surface trafficking of excitatory N-methyl-D-aspartate (NMDA) receptors. Here we have investigated the interactions and surface trafficking of NR1-1a/NR2A and NR1-1a/NR2B NMDA receptor subtypes with three APP mutations linked to familial Alzheimer's disease, APP695(Indiana), APP695(London) and APP695(Swedish). Flag-tagged mutated APP695s were generated and shown to be expressed at equivalent levels to wild-type APP695 in mammalian cells. Each APP mutant co-precipitated with NR1-1a/NR2A and NR1-1a/NR2B receptors following co-expression in mammalian cells. Further, as found for wild-type APP695, each enhanced NMDA receptor surface expression with no concomitant increase in total NR1-1a, NR2A or NR2B subunit expression. Thus these three familial APP mutations behave as wild-type APP695 with respect to their association with assembled NMDA receptors and their APP695-enhanced receptor cell surface trafficking.
authors.affiliation: University College London School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Neal
authors.initials: N
authors.lastname: Innocent
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Cousins
authors.forename: F Anne
authors.initials: FA
authors.lastname: Stephenson
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate