Year: 2009
Type: article
Abstract: The processing of amyloid precursor protein (APP) to Abeta is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood. Our previous work has shown that APP processing and Abeta 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 alpha3beta1 integrin, and alpha3beta1 integrin altered APP trafficking and processing. Addition of an alpha3beta1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development.
Source: Journal of Neuroscience
Authors: H.-S. Hoe, K. J. Lee, R. S. E. Carney, J. Lee, A. Markova, J.-Y. Lee, B. W. Howell, B. T. Hyman, D. T. S. Pak, G. Bu, G. W. Rebeck
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Awards: ApoE Receptor Biology and Neurodegeneration, Fyn modulation of APP processing, ApoE pathway in cerebrovascular Aβ clearance in Alzheimer's disease, APOE AND ITS RECEPTORS IN NORMAL AND ALZHEIMERS BRAIN, LRP AND ALZHEIMER'S DISEASE, Molecular mechanisms of synapse lose by polo kinases, ApoE and ApoE receptors in the molecular mechanisms of synapse formation, Apolipoprotein E receptors and Alzheimers disease, G7856023117, ApoE and LRP1 in brain insulin signaling and glucose metabolism (Competitive Renewal)
OpenAlex ID: W2147636813