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Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1.

http://www.ncbi.nlm.nih.gov/pubmed/16301330

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.

Pubmed ID: 16301330 RIS Download

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

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Associated grants

  • Agency: NIGMS NIH HHS, Id: 5R01GM068596-02
  • Agency: NIA NIH HHS, Id: AG08012
  • Agency: NIGMS NIH HHS, Id: R01 GM068596

GO (Data, Gene Annotation)

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