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.
Lee
Yong
Y
National Research Laboratory of Neurobiology, School of Biological Sciences, Seoul National University, Seoul, Korea.
Chang
Deok-Jin
DJ
Lee
Yong-Seok
YS
Chang
Keun-A
KA
Kim
Hyoung
H
Yoon
Jeung-Sook
JS
Lee
Seungbok
S
Suh
Yoo-Hun
YH
Kaang
Bong-Kiun
BK
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins; D009865:Oocytes / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats; D014162:Transfection; D014981:Xenopus / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D008565:Membrane Proteins; C431143:TM2D1 protein, human; D019204:GTP-Binding Proteins