DAB1 and reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing

Hyang Sook Hoe, Tracy S. Tran, Yasuji Matsuoka, Brian W. Howell, G. William Rebeck

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


Numerous cytoplasmic adaptor proteins, including JIP1, FE65, and X11α, affect amyloid precursor protein (APP) processing and Aβ production. Dab1 is another adaptor protein that interacts with APP as well as with members of the apoE receptor family. We examined the effect of Dab1 on APP and apoEr2 processing in transfected cells and primary neurons. Dab1 interacted with APP and apoEr2 and increased levels of their secreted extracellular domains and their cytoplasmic C-terminal fragments. These effects depended on the NPXY domains of APP and apoEr2 and on the phosphotyrosine binding domain of Dab1 but did not depend on phosphorylation of Dab1. Dab1 decreased the levels of APP β-C-terminal fragment and secreted Aβ. Full-length Dab1 or its phosphotyrosine binding domain alone increased surface levels of APP, as determined by surface protein biotinylation and live cell staining. A ligand for apoEr2, the extracellular matrix protein Reelin, significantly increased the interaction of apoEr2 with Dab1. Surprisingly, we also found that Reelin treatment significantly increased the interaction of APP and Dab1. Moreover, Reelin treatment increased cleavage of APP and apoEr2 and decreased production of the β-C-terminal fragment of APP and Aβ. Together, these data suggest that Dab1 alters trafficking and processing of APP and apoEr2, and this effect is influenced by extracellular ligands.

Original languageEnglish (US)
Pages (from-to)35176-35185
Number of pages10
JournalJournal of Biological Chemistry
Issue number46
StatePublished - Nov 17 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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