Abstract
APP is a transmembrane precursor of beta-amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of normal wild-type APP (wtAPP). Treatment of neuronal F11 cells, immortalized embryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies caused death. Death was not induced by antibody in parental F11 cells. Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in primary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study provides a novel insight into the normal and pathological functions of cell-surface wtAPP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / immunology*
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Alzheimer Disease / metabolism
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Alzheimer Disease / physiopathology
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Amyloid beta-Protein Precursor / drug effects
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Amyloid beta-Protein Precursor / immunology
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Antibodies / immunology
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Antibodies / metabolism
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Antibodies / toxicity*
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Antibody Specificity / immunology
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Apoptosis / drug effects
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Apoptosis / immunology*
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Cell Count / statistics & numerical data
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Cell Line, Transformed / drug effects*
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Cell Line, Transformed / immunology
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Cell Line, Transformed / metabolism
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Cysteine Proteinase Inhibitors / pharmacology
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Fetus
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In Situ Nick-End Labeling / statistics & numerical data
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Membrane Proteins / drug effects
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Membrane Proteins / immunology
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Membrane Proteins / metabolism*
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Neurotoxins / immunology
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Neurotoxins / metabolism
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Neurotoxins / pharmacology*
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Oligopeptides / pharmacology
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Pertussis Toxin
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Protein Structure, Tertiary / drug effects
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Protein Structure, Tertiary / physiology
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Rats
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Virulence Factors, Bordetella / pharmacology
Substances
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Amyloid beta-Protein Precursor
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Antibodies
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Cysteine Proteinase Inhibitors
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Membrane Proteins
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Neurotoxins
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Oligopeptides
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Virulence Factors, Bordetella
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acetyl-aspartyl-glutamyl-valyl-aspartal
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Pertussis Toxin