Extra ViEw www.landesbioscience.com tissue Barriers e28127-1

Extra ViEw The Hippo signaling pathway regu-lates a number of cellular events, including the control of cell fates in pre-implantation mouse embryos. The inner and outer cells of the embryo show high and low levels of Hippo signaling, respec-tively. This position-dependent Hippo signaling promotes the specification of distinct cell fates. In a recent paper, we identified the molecular mechanism that controls Hippo signaling in preimplan-tation embryos. The junction-associated scaffold protein angiomotin (Amot) plays a key role in this mechanism. At the adherens junctions of the inner cells, Amot activates the Hippo pathway by recruiting and activating the protein kinase large tumor suppressor (Lats). In contrast, Amot at the apical membrane of the outer cells suppresses Hippo sig-naling by interacting with F-actin. The phosphorylation of Amot inhibits its interaction with F-actin and activates Hippo signaling. We propose that Amot acts as a molecular switch for the Hippo pathway and links F-actin with Lats activity