Antibody-regulated neurotoxic function of cell-surface beta-amyloid precursor protein.
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.
Sudo
H
H
Department of Pharmacology and Neurosciences, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, 160, Japan.
Jiang
H
H
Yasukawa
T
T
Hashimoto
Y
Y
Niikura
T
T
Kawasumi
M
M
Matsuda
S
S
Takeuchi
Y
Y
Aiso
S
S
Matsuoka
M
M
Murayama
Y
Y
Nishimoto
I
I
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D000918:Antibody Specificity / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002452:Cell Count / Q000706:statistics & numerical data; D002461:Cell Line, Transformed / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005333:Fetus; D020287:In Situ Nick-End Labeling / Q000706:statistics & numerical data; D008565:Membrane Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009498:Neurotoxins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D037342:Pertussis Toxin; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D009498:Neurotoxins; D009842:Oligopeptides; D010566:Virulence Factors, Bordetella; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D037342:Pertussis Toxin