Amyloid β protein precursor (AβPP), but not AβPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1

Shuji Matsuda, Yukiko Matsuda, Luciano D'Adamio

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Proteolytic processing of amyloid β protein precursor (AβPP) generates peptides that regulate normal cell signaling and are implicated in Alzheimer's disease pathogenesis. AβPP processing also occurs in nerve processes where AβPP is transported from the cell body by kinesin-I, a microtubule motor composed of two kinesin heavy chain and two kinesin light chain (Klc) subunits. AβPP transport is supposedly mediated by the direct AβPP-Klc1 interaction. Here we demonstrate that the AβPP-Klc1 interaction is not direct but is mediated by JNK-interacting protein J (JIP1). The phosphotyrosine binding domain of JIP1 binds the cytoplasmic tail of AβPP, whereas the JIP1 C-terminal region interacts with the tetratrico-peptide repeats of Klc1. We also show that JIP1 does not bridge the AβPP gene family member AβPP-like protein 2, APLP2, to Klc1. These results support a model where JIP1 mediates the interaction of AβPP to the motor protein kinesin-I and that this JIP1 function is unique for AβPP relative to its family member APLP2. Our data suggest that kinesin-II-dependent neuronal AβPP transport, which controls AβPP processing, may be regulated by JIP1.

Original languageEnglish (US)
Pages (from-to)38601-38606
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number40
DOIs
StatePublished - Oct 3 2003
Externally publishedYes

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Kinesin
Amyloid beta-Protein Precursor
Scaffolds
Proteins
Protein Transport
kinesin light-chain proteins
Processing
Cell signaling
Peptides
Phosphotyrosine
Microtubules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Amyloid β protein precursor (AβPP), but not AβPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1. / Matsuda, Shuji; Matsuda, Yukiko; D'Adamio, Luciano.

In: Journal of Biological Chemistry, Vol. 278, No. 40, 03.10.2003, p. 38601-38606.

Research output: Contribution to journalArticle

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