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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AG023990-02
Application #
6867433
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Snyder, Stephen D
Project Start
2004-03-01
Project End
2005-06-15
Budget Start
2005-03-01
Budget End
2005-06-15
Support Year
2
Fiscal Year
2005
Total Cost
$12,190
Indirect Cost
Name
Emory University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Volpicelli-Daley, Laura A; Li, Yawei; Zhang, Chun-Jiang et al. (2005) Isoform-selective effects of the depletion of ADP-ribosylation factors 1-5 on membrane traffic. Mol Biol Cell 16:4495-508