Vesicular transport of the amyloid precursor protein

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): One of the primary characteristics of Alzheimer's disease (AD) is senile plaques containing Ab which is formed by the processing of amyloid precursor protein (APP). Intracellular transport plays a crucial role in APP processing, but the mechanisms involved in controlling APP intracellular traffic remain insufficiently characterized. Two proteins, Mints and FE65 play opposite roles in APP processing: Mints inhibit and FE65 increases the production of Ab. Recent data suggest that Mints may function as a vesicular coat protein and thus Mints may regulate APP processing by controlling APP traffic. This proposal will establish biochemical assays that will define the molecular components involved APP vesicular trafficking. Membrane recruitment assays will be used to test the hypothesis that APP acts as a cargo receptor that recruits Mints to the membrane in an ARF-dependent manner that is prevented by FE65. In vitro budding assays will be performed to determine if the budding of APP-containing vesicles requires ARF and Mints. Because APP processing depends on APP trafficking, these data will elucidate the mechanisms by which APP is targeted to a nonpathogenic pathway and consequently identify novel therapeutic targets for AD.