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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.

Pubmed ID: 16301330

Authors

  • Muresan Z
  • Muresan V

Journal

The Journal of cell biology

Publication Data

November 21, 2005

Associated Grants

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

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