Actin up for Hippo.

The Hippo (Hpo) signalling pathway is an evolutionarily conserved pathway controlling tissue growth, but its upstream inputs remain poorly understood. In this issue of The EMBO Journal, Sansores-Garcia et al (2011) report that modulation of filamentous (F)-actin accumulation controls Hpo pathway activity. In a related study, GarciaFernandez et al (2011) confirm this finding, and also show that the Hpo pathway itself can modulate F-actin levels. Such actin-dependent regulation of Hpo pathway activity has relevance to the control of tissue growth by epithelial architecture and external tension cues. Over the last 10 years, the Hpo signalling pathway has emerged as a key negative regulator of tissue growth in Drosophila and mammalian systems (reviewed by Harvey and Tapon (2007)). Central to the Hpo pathway is the Hpo protein kinase and its adaptor, Salvador (Sav), along with the Warts (Wts) kinase and its adaptor Mats (see Figure 1). Activated Hpo phosphorylates and activates Wts, which in turn phosphorylates the transcriptional co-activator Yki, rendering it inactive and restricted to the cytoplasm. Upon inactivation of the Hpo pathway, Yki is dephosphorylated and can enter the nucleus where, in complex with the Scalloped (Sd) Tead-family transcription factor, it upregulates target genes, including the cell-cycle regulator Cyclin E and the inhibitor of apoptosis Diap1. The core Hpo kinase cassette is regulated by several upstream inputs, including the KEM complex, consisting of Expanded (Ex), Merlin (Mer) and Kibra (Kib), the atypical cadherin Fat (Ft), and the apicobasal polarity regulators, Crumbs (Crb), atypical protein kinase C (aPKC) and Lethal-giant-larvae (Lgl) (reviewed by