Beta-secretase (BACE) and GGA1 interaction in cells is dependent on BACE phosphorylation

Amyloid-beta peptide, which accumulates in senile plaques in Alzheimer's disease (AD), is derived from the amyloid precursor protein (APP)by cleavage of Beta-secretase (BACE), transmembrane aspartic proteinase and consequently Gamma-secretase. Since a majority of BACE cleavage activity occurs in endosomes, signals regulating its trafficking to these compartments are important to understand AD pathogenesis. Golgi-localized, gamma-ear-containing ARF binding (GGA) proteins, which are involved in sorting proteins to endosomes, are binding by their VHS-domain to a DISLL sequence in the BACE C-tail. In isolated protei…