Dab1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing

Oh Yeun Kwon, Kyounghee Hwang, Jeom A. Kim, Kwangmyung Kim, Ick Chan Kwon, Hyun Kyu Song, Hyesung Jeon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Fe65 and Dab1 are adaptor proteins that interact with the cytoplasmic domain of amyloid precursor protein (APP) via phosphotyrosine-binding (PTB) domain and that affect APP processing and Ab production. Co-expression of Dab1 with Fe65 and APP resumed nuclear translocation of Fe65 despite of its cytoplasmic anchor, APP. The decreased amount of Fe65 bound to APP was shown in co-immunoprecipitation assay from the cells with Dab1 which also displayed the effect on APP processing. These data suggested that Fe65 and Dab1 compete for binding to APP. Surprisingly, we found that Fe65 interacts with Dab1 via C-terminal region of Dab1 and unphosphorylated Dab1 is capable of binding Fe65. Dab1 interacts with the low-density lipoprotein receptor-related protein (LRP) as well as APP through its PTB domain. Dab1 significantly decreased the amount of APP bound to LRP and the level of secreted APP and APP-CTF in LRP expressing cells, unlike Fe65. It implies that overexpression of Dab1 diminish LRP-APP complex formation, resulting in altered APP processing. The competition for overlapped binding site among adaptor proteins may be related to the regulation mechanism of APP metabolism in various conditions.

Original languageEnglish
Pages (from-to)508-519
Number of pages12
JournalJournal of Cellular Biochemistry
Volume111
Issue number2
DOIs
Publication statusPublished - 2010 Oct 1

Fingerprint

Amyloid beta-Protein Precursor
Processing
Lipoprotein Receptors
Phosphotyrosine
Proteins
LDL-Receptor Related Proteins
LDL Receptors
Immunoprecipitation
Anchors

Keywords

  • APP processing
  • Dab1
  • Fe65
  • LRP
  • NPTY motif
  • Phosphotyrosine-binding domain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Dab1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing. / Kwon, Oh Yeun; Hwang, Kyounghee; Kim, Jeom A.; Kim, Kwangmyung; Kwon, Ick Chan; Song, Hyun Kyu; Jeon, Hyesung.

In: Journal of Cellular Biochemistry, Vol. 111, No. 2, 01.10.2010, p. 508-519.

Research output: Contribution to journalArticle

Kwon, Oh Yeun ; Hwang, Kyounghee ; Kim, Jeom A. ; Kim, Kwangmyung ; Kwon, Ick Chan ; Song, Hyun Kyu ; Jeon, Hyesung. / Dab1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing. In: Journal of Cellular Biochemistry. 2010 ; Vol. 111, No. 2. pp. 508-519.
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