Interaction of Reelin with amyloid precursor protein promotes neurite outgrowth

Hyang Sook Hoe, Joo Lee Kea, Rosalind S.E. Carney, Jiyeon Lee, Alexandra Markova, Ji Yun Lee, Brian W. Howell, Bradley T. Hyman, Daniel T.S. Pak, Guojun Bu, G. William Rebeck

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

The processing of amyloid precursor protein (APP) to Aβ is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APPis not well understood. Our previous work has shown that APP processing and Aβ production are regulated by the extracellular matrix protein Reelin. In the present study, we examined whether Reelin interacts with APP, and the functional consequences of that interaction in vitro. Using coimmunoprecipitation, we found that Reelin interacted with APP through the central domain of Reelin (repeats 3-6) and the E1 extracellular domain of APP. Reelin increased cell surface levels of APP and decreased endocytosis of APP in hippocampal neurons in vitro. In vivo, Reelin levels were increased in brains of APP knock-out mice and decreased in APP-overexpressing mice. RNA interference knockdown of APP decreased neurite outgrowth in vitro and prevented Reelin from increasing neurite outgrowth. Knock-out of APP or Reelin decreased dendritic arborization in cortical neurons in vivo, and APP overexpression increased dendritic arborization. APP and Reelin have previously been shown to promote neurite outgrowth through interactions with integrins. We confirmed that APP interacted with α3β1 integrin, and α3β1 integrin altered APP trafficking and processing. Addition of an α3β1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development.

Original languageEnglish (US)
Pages (from-to)7459-7473
Number of pages15
JournalJournal of Neuroscience
Volume29
Issue number23
DOIs
StatePublished - Jun 10 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hoe, H. S., Kea, J. L., Carney, R. S. E., Lee, J., Markova, A., Lee, J. Y., Howell, B. W., Hyman, B. T., Pak, D. T. S., Bu, G., & Rebeck, G. W. (2009). Interaction of Reelin with amyloid precursor protein promotes neurite outgrowth. Journal of Neuroscience, 29(23), 7459-7473. https://doi.org/10.1523/JNEUROSCI.4872-08.2009