Angiomotins link Hippo signaling to the actin cytoskeleton.

Cells rapidly remodel their actin cytoskeleton to deal with external forces and changes in their mechanical environment. Hippo signaling is strongly regulated by changes in actin organization. Thus one way that the Hippo pathway senses the mechanical environment appears to be through monitoring the actin cytoskeleton. How Hippo signaling senses and responds to changes in the actin cytoskeleton has remained uncertain. We identified angiomotins as novel Hippo pathway scaffolding proteins that are capable of interacting with both F-actin and multiple core components of the signaling network. Angiomotins inhibit YAP, a transcriptional co-activator that is the primary effector of Hippo signaling through two mechanisms; directly binding YAP and sequestering it in the cytoplasm, and by activating the YAP inhibitory kinase LATS. We showed that F-actin and YAP compete for binding to angiomotins rendering angiomotin inhibition of YAP sensitive to F-actin levels. These studies revealed one mechanism by which F-actin levels control Hippo signaling. Ongoing studies in the lab focus on how angiomotins activate LATS, whether this activation is regulated by F-actin, and whether other mechanisms operate to link Hippo signaling to F-actin organization.  

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