Phase separation of Hippo signalling complexes

Teresa T. Bonello, Danfeng Cai, Georgina C. Fletcher, Kyler Wiengartner, Victoria Pengilly, Kimberly S. Lange, Zhe Liu, Jennifer Lippincott-Schwartz, Jennifer M. Kavran, Barry J. Thompson

Research output: Contribution to journalArticlepeer-review


The Hippo pathway was originally discovered to control tissue growth in Drosophila and includes the Hippo kinase (Hpo; MST1/2 in mammals), scaffold protein Salvador (Sav; SAV1 in mammals) and the Warts kinase (Wts; LATS1/2 in mammals). The Hpo kinase is activated by binding to Crumbs-Expanded (Crb-Ex) and/or Merlin-Kibra (Mer-Kib) proteins at the apical domain of epithelial cells. Here we show that activation of Hpo also involves the formation of supramolecular complexes with properties of a biomolecular condensate, including concentration dependence and sensitivity to starvation, macromolecular crowding, or 1,6-hexanediol treatment. Overexpressing Ex or Kib induces formation of micron-scale Hpo condensates in the cytoplasm, rather than at the apical membrane. Several Hippo pathway components contain unstructured low-complexity domains and purified Hpo-Sav complexes undergo phase separation in vitro. Formation of Hpo condensates is conserved in human cells. We propose that apical Hpo kinase activation occurs in phase separated “signalosomes” induced by clustering of upstream pathway components.

Original languageEnglish (US)
Article numbere112863
JournalEMBO Journal
Issue number6
StatePublished - Mar 15 2023


  • Hippo signalling
  • condensates
  • epithelia
  • mechanobiology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Molecular Biology
  • Neuroscience(all)


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