beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module

• Published in: The Journal of biological chemistry Vol. 276; no. 22; pp. 18748 - 18756
• Main Authors: Kajkowski, E M, Lo, C F, Ning, X, Walker, S, Sofia, H J, Wang, W, Edris, W, Chanda, P, Wagner, E, Vile, S, Ryan, K, McHendry-Rinde, B, Smith, S C, Wood, A, Rhodes, K J, Kennedy, J D, Bard, J, Jacobsen, J S, Ozenberger, B A
• Format: Journal Article
• Language: English
• Published: United States 01.06.2001
• Subjects: Alzheimer Disease - metabolism; Amino Acid Sequence; Amyloid beta-Peptides - metabolism; Apoptosis; Binding Sites; Binding, Competitive; Blotting, Northern; Brain - metabolism; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Caspases - metabolism; Cell Line; Cell Membrane - metabolism; Cells, Cultured; Conserved Sequence; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Gene Library; GTP-Binding Proteins - metabolism; Humans; Immunoblotting; In Situ Hybridization; Kinetics; Membrane Proteins; Models, Biological; Molecular Sequence Data; Mutation; Neurons - metabolism; Peptides - metabolism; Protein Binding; Protein Biosynthesis; Protein Structure, Tertiary; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Signal Transduction; Tissue Distribution; Two-Hybrid System Techniques
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M011161200

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.