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

Zoia Muresan, Virgil Muresan

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

The transmembrane protein amyloid-β precursor protein (APP) and the vesicle-associated protein c-Jun NH2-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 Thr668-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.

Original languageEnglish (US)
Pages (from-to)615-625
Number of pages11
JournalJournal of Cell Biology
Volume171
Issue number4
DOIs
StatePublished - Nov 21 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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