β-amyloid peptide binding protein does not couple to G protein in a heterologous Xenopus expression system

Abstract

Alzheimer's disease is a neurodegenerative disorder related to the formation of protein aggregates. -Amyloid protein (A), generated by enzymatic cleavage of amyloid precursor protein (APP), can cause such aggregation, and these aggregates may cause neuronal cell death by inducing apoptosis. However, A-induced intracellular signaling pathways involved in the neuronal death are not well understood. Recently it was shown that A aggregates induce neuronal cell death via -amyloid peptide-binding protein (BBP), a receptor for A in BBP-transfected cells, which is known to be sensitive to pertussis toxin, a Gi/o family inhibitor. However, the actual coupling of BBP to the pertussis-sensitive G protein was not demonstrated. In this study, we performed electrophysiological recordings using the two-electrode voltage-clamp technique to test whether human or Drosophila BBPs, singly or in combination with APP, are coupled to a specific type of G protein. Our results suggest that BBP is not directly coupled to Gi/o, Gs, or Gq proteins and that BBP may need a component other than APP to exert its toxic effect in concert with Aβ.