Molecular functions of CORO7 in regulating Hippo signaling pathway

Abstract

From Drosophila to mammals, the Hippo pathway plays crucial roles in control of organ growth and tissue homeostasis. Through rigorous studies for the last two decades, the core kinase cassette comprised of two kinases (MST1/2 and LATS1/2) and two scaffolds (SAV1 and MOB1) has been discovered to be essential for the regulation of Hippo signaling. However, how and where its formation and activation happens are not fully understood. Here, I identify that CORO7 positively regulates the Hippo pathway through the analysis of protein interaction database and genetic screening in Drosophila. I demonstrate that CORO7 is necessary for Hippo signaling activation induced by serum deprivation, contact inhibition and cytoskeleton damage. I also show that CORO7 physically interacts with Hippo core components and functions as a scaffold for the core kinase cassette. Interaction of CORO7 with SAV1 and MST1/2 is regulated by Hippo activating signals, suggesting a multi-step binding regulation of Hippo core kinase cassette by CORO7. My results provide molecular insights of Hippo signaling regulation and have implications for understanding Hippo-related diseases.