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

Alzheimer's disease is a neurodegenerative disorder related to the formation of protein aggregates. beta-Amyloid protein (A beta), 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 beta-induced intracellular signaling pathways involved in the neuronal death are not well understood. Recently it was shown that A beta aggregates induce neuronal cell death via beta-amyloid peptide-binding protein (BBP), a receptor for A beta in BBP-transfected cells, which is known to be sensitive to pertussis toxin, a G alpha(i/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 G alpha(i/o), G alpha(s), or G alpha(q) proteins and that BBP may need a component other than APP to exert its toxic effect in concert with A beta.

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