Ligand-dependent G protein coupling function of amyloid transmembrane precursor.
Amyloid precursor protein (APP), a transmembrane precursor of beta-amyloid, possesses a function whereby it associates with G(o) through its cytoplasmic His657-Lys676. Here we demonstrate that APP has a receptor function. In phospholipid vesicles consisting of baculovirally made APP695 and brain trimeric G(o), 22C11, a monoclonal antibody against the extracellular domain of APP, increased GTP gamma S binding and the turnover number of GTPase of G(o) without affecting its intrinsic GTPase activity. This effect of 22C11 was specific among various antibodies and was observed neither in G(o) vesicles nor in APP695/Gi2 vesicles. In APP695/G(o) vesicles, synthetic APP66-81, the epitope of 22C11, competitively antagonized the action of 22C11. Monoclonal antibody against APP657-676, the G(o) binding domain of APP695, specifically blocked 22C11-dependent activation of G(o). Therefore, APP has a potential receptor function whereby it specifically activates G(o) in a ligand-dependent and ligand-specific manner.
Okamoto
T
T
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown.
Takeda
S
S
Murayama
Y
Y
Ogata
E
E
Nishimoto
I
I
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008024:Ligands; D011485:Protein Binding; D018411:Spodoptera
D016564:Amyloid beta-Protein Precursor; D008024:Ligands; D019204:GTP-Binding Proteins