Expanded directly binds conserved regions of Fat to restrain growth via the Hippo pathway

Alexander D. Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V. Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen McNeill

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes loss of apical Expanded and promotes tissue overgrowth. Unexpectedly, we find Fat can bind its ligand Dachsous via interactions of their cytoplasmic domains, in addition to the known extracellular interactions. Importantly, Expanded is stabilized by Fat independently of Dachsous binding. These data provide new mechanistic insights into how Fat regulates Expanded, and how Hippo signaling is regulated during organ growth.

Original languageEnglish
JournalThe Journal of cell biology
Volume222
Issue number5
DOIs
StatePublished - May 1 2023

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