NMDA receptor/amyloid precursor protein interactions: A comparison between wild-type and amyloid precursor protein mutations associated with familial Alzheimer's disease

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• 作者：Neal Innocent ; Sarah L. Cousins ; F. Anne Stephenson ; ^{anne.stephenson@pharmacy.ac.uk}
• 关键词：A尾 ; amyloid-尾 peptides ; apoEr2 ; apolipoprotein E receptor 2 ; APP ; amyloid precursor protein ; ELISA ; enzyme linked immunoadsorbent assay ; NMDA ; N-methyl-d-aspartate ; NR1 ; NR2A ; etc.NMDA receptor NR1 subunit ; NR2A subunit ; etc. ; PBS ; phosphate buffered ; P
• 刊名：Neuroscience Letters
• 出版年：2012
• 期刊代码：52_03043940
• 类别：neu
• 出版时间：2 May, 2012
• 卷：515
• 期：2
• 页码：131-136
• 文件大小：668 K

摘要

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.