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

J Biol Chem. 2001 Jun 1;276(22):18748-56. doi: 10.1074/jbc.M011161200. Epub 2001 Feb 20.

Abstract

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.

MeSH terms

  • 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
  • GTP-Binding Proteins / metabolism*
  • Gene Library
  • 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

Substances

  • Amyloid beta-Peptides
  • Carrier Proteins
  • DNA, Complementary
  • Membrane Proteins
  • Peptides
  • Recombinant Proteins
  • TM2D1 protein, human
  • Tm2d1 protein, mouse
  • Caspases
  • GTP-Binding Proteins

Associated data

  • GENBANK/AF353990
  • GENBANK/AF353991
  • GENBANK/AF353992
  • GENBANK/AF353993