GGA1 overexpression alters trafficking and subcellular distribution of the amyloid precursor protein

Background: The amyloid precursor protein (APP) is cleaved by two sequential proteases, first BACE (beta-site of APP-cleaving enzyme) followed by Gamma-secretase to release the A-beta peptides, that accumulate in the senile plaques in Alzheimer's disease (AD) and the APP intracellular domain (AICD). APP and BACE traffic together. GGA1, a member of the Golgi-localized gamma-ear-containing ARF binding (GGA) protein family interacts with BACE phosphorylation dependent via its VHS domain in the Golgi and influences its subcellular distribution. Objective: We postulated therefore that GGA might also interact with APP…