beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module.
Degeneration of neurons in Alzheimer's disease is mediated by beta-amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta-amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta-amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta-amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta-amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.
Kajkowski
E M
EM
Wyeth Neuroscience, Wyeth-Ayerst Research, CN 8000, Princeton, New Jersey 08543-8000, USA.
Lo
C F
CF
Ning
X
X
Walker
S
S
Sofia
H J
HJ
Wang
W
W
Edris
W
W
Chanda
P
P
Wagner
E
E
Vile
S
S
Ryan
K
K
McHendry-Rinde
B
B
Smith
S C
SC
Wood
A
A
Rhodes
K J
KJ
Kennedy
J D
JD
Bard
J
J
Jacobsen
J S
JS
Ozenberger
B A
BA
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D017209:Apoptosis; D001665:Binding Sites; D001667:Binding, Competitive; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D007700:Kinetics; D008565:Membrane Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D010455:Peptides; D011994:Recombinant Proteins; C431143:TM2D1 protein, human; C486608:Tm2d1 protein, mouse; D020169:Caspases; D019204:GTP-Binding Proteins