Regulation of the physiological function and metabolism of AbetaPP by AbetaPP binding proteins.
Amyloid-beta protein precursor (AbetaPP) is a receptor-like, type-I membrane protein that plays a central role in the pathogenesis of Alzheimer's disease. The cytoplasmic domain of AbetaPP is important for the metabolism and physiological functions of AbetaPP and contains a GYENPTY motif that interacts with proteins that contain a phosphotyrosine binding (PTB) domain such as X11/Mint, FE65, and the JIP family of proteins. X11 and X11-like proteins are neuronal adaptor proteins involved in presynaptic function and the intracellular trafficking of proteins. Recent studies in X11s knockout mice confirmed findings from in vitro studies that X11 proteins affect AbetaPP metabolism and the generation of amyloid-beta peptide. FE65 proteins are involved in transactivation in coordination with the intracellular domain fragment of AbetaPP, and/or in cellular responses to DNA damage. Neurodevelopmental defects observed in FE65s double knockout mice suggest that FE65 proteins cooperate with AbetaPP to play a role in neuronal cytoskeletal regulation. c-Jun N-terminal kinase (JNK) interacting protein-1 (JIP-1), a scaffolding protein for the JNK kinase cascade, has been suggested to mediate the intracellular trafficking of AbetaPP by molecular motor kinesin-1. This article reviews some of the recent findings regarding the regulation of physiological function and metabolism of AbetaPP by AbetaPP binding proteins.
Taru
Hidenori
H
Creative Research Institution Sousei, Hokkaido University, Kita-ku, Sapporo, Japan. taru@cris.hokudai.ac.jp
Suzuki
Toshiharu
T
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000145:classification / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins