Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1.
The transmembrane protein amyloid-beta precursor protein (APP) and the vesicle-associated protein c-Jun NH(2)-terminal kinase-interacting protein-1 (JIP-1) are transported into axons by kinesin-1. Both proteins may bind to kinesin-1 directly and can be transported separately. Because JIP-1 and APP can interact, kinesin-1 may recruit them as a complex, enabling their cotransport. ... In this study, we tested whether APP and JIP-1 are transported together or separately on different vesicles. We found that, within the cellular context, JIP-1 preferentially interacts with Thr(668)-phosphorylated APP (pAPP), compared with nonphosphorylated APP. In neurons, JIP-1 colocalizes with vesicles containing pAPP and is excluded from those containing nonphosphorylated APP. The accumulation of JIP-1 and pAPP in neurites requires kinesin-1, and the expression of a phosphomimetic APP mutant increases JIP-1 transport. Down-regulation of JIP-1 by small interfering RNA specifically impairs transport of pAPP, with no effect on the trafficking of nonphosphorylated APP. These results indicate that the phosphorylation of APP regulates the formation of a pAPP-JIP-1 complex that accumulates in neurites independent of nonphosphorylated APP.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amyloid beta-Protein Precursor, Animals, Axons, Bacterial Proteins, Biological Transport, Biotinylation, Blotting, Western, Brain, COS Cells, Cell Line, Cell Movement, Cercopithecus aethiops, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Immunoprecipitation, Kinesin, Luminescent Proteins, Mice, Microscopy, Fluorescence, Mutation, Neurites, Neurons, Phosphorylation, Protein Binding, Protein Structure, Tertiary, RNA Interference, RNA, Small Interfering, Signal Transduction, Transfection
Adaptor Proteins, Signal Transducing, Amyloid beta-Protein Precursor, Animals, Axons, Bacterial Proteins, Biological Transport, Biotinylation, Blotting, Western, Brain, COS Cells, Cell Line, Cell Movement, Cercopithecus aethiops, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Immunoprecipitation, Kinesin, Luminescent Proteins, Mice, Microscopy, Fluorescence, Mutation, Neurites, Neurons, Phosphorylation, Protein Binding, Protein Structure, Tertiary, RNA Interference, RNA, Small Interfering, Signal Transduction, Transfection
J. Cell Biol.
Date: Nov. 21, 2005
PubMed ID: 16301330
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