The paper
T. Liu et al., “The amyloid precursor protein is a conserved Wnt receptor,” eLife, 10:e69199, 2021.
Amyloid precursor protein, which generates amyloid-β when broken down, has long been associated with Alzheimer’s disease. But its normal function in the brain has remained relatively mysterious. Over the past decade, Bassem Hassan of the Paris Brain Institute and others have found hints that the protein (APP) is part of a complex involved in Wnt signaling—an evolutionarily conserved pathway that regulates animal development—as well as in synaptic plasticity and adult neurogenesis.
Studying human APP and the Drosophila homolog APPL in vitro, Hassan’s team now reports that these membrane proteins bind directly to two types of Wnt peptides, Wnt3a and Wnt5a, in a way that regulates intracellular APP levels: Wnt3a increases APP’s stability and enhances its persistence, while Wnt5a promotes its breakdown. “It looks like they’re acting opposite to one another,” Hassan says, adding ...
