Beta-amyloid peptide-induced apoptosis regulated by a novel protein containing a G protein activation module.
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.
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.