Courtesy of Science/AAAS
Using yeast cells, a team of Whitehead scientists in the lab of Whitehead Member Susan Lindquist investigated the harmful effects of amyloid beta (Aβ), a peptide whose accumulation in amyloid plaques is a hallmark of AD. Work by the lab indicates that Aβ disrupts normal cellular trafficking, with clathrin-mediated endocytosis being specifically vulnerable. Under normal conditions, the membrane bound receptor Ste3 (green) is subject to clathrin-mediated endocytosis and is trafficked to the cell’s vacuole (left). In Aβ expressing yeast cells, Ste3 is not localized to the vacuole, but is dispersed in foci throughout the cell, indicating that endocytic trafficking is perturbed (center). Expression of the yeast homolog of PICALM, one of the most highly validated human AD risk factors, restores normal trafficking in Aβ-expressing yeast, and Ste3 is again localized in the vacuole (right).