Interaction of the Cytosolic Domains of sorLA/LR11 with the Amyloid Precursor Protein (APP) and β-Secretase β-Site APP-Cleaving Enzyme

• DOI: 10.1523/jneurosci.3882-05.2006
• Publication Date: 2006-01-11T22:20:11Z
• Authors: Robert Spoelgen; Christine A. F. v...; Anne V. Thomas; Ithan D. Peltan; Mirjam Koker; Amy Deng; Michael C. Irizarry; Olav M. Andersen; Thomas E. Willnow; Bradley T. Hyman
• Keywords: Cleavage (geology)

sorLA is a recently identified neuronal receptor for amyloid precursor protein (APP) that known to interact with APP and affect its intracellular transport processing. Decreased levels of in the brain Alzheimer's disease (AD) patients elevated amyloid-β peptide (Aβ) sorLA-deficient mice point importance this neurodegenerative disorder. We analyzed cleavage an APP-shedding assay found both and, surprisingly, tail construct inhibited β-site APP-cleaving enzyme (BACE)-dependent manner. In line finding, significantly reduced secreted Aβ when BACE was overexpressed, suggesting influencesβ-cleavage. To understand effect on by BACE, we whether interacts and/or BACE. Because full-length C-terminal constructs were functionally relevant processing, sorLA–APP potential cytoplasmatic interaction domain. C99 coimmunoprecipitated, pointing toward existence new site between APP. Moreover, also coimmunoprecipitate. Thus, might therefore directly BACE–APP complex formation. test impacts interactions, used fluorescence resonance energy transfer evaluate interactions cells. discovered Golgi. postulate acts as trafficking prevents hence