Golgi Associated Gamma Adaptin Ear Containing ARF Binding Protein 3 (GgA3)

GGA3 encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. As GGA3 was removed by caspase cleavage, BACE was stabilized, leading to elevated beta-secretase cleavage of APP. Silencing of GGA3 by RNA interference led to increased levels of BACE and the APP cleavage products C99 and A-beta. GGA3 protein levels were significantly decreased and were inversely correlated with BACE levels in AD brains, but not in nondemented control brains.