Multiphase coalescence mediates Hippo pathway activation

Li Wang, Kyungsuk Choi, Ting Su, Bing Li, Xiaofeng Wu, Ruihui Zhang, Jordan H. Driskill, Hongde Li, Huiyan Lei, Pengfei Guo, Elizabeth H. Chen, Yonggang Zheng, Duojia Pan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The function of biomolecular condensates is often restricted by condensate dissolution. Whether condensates can be suppressed without condensate dissolution is unclear. Here, we show that upstream regulators of the Hippo signaling pathway form functionally antagonizing condensates, and their coalescence into a common phase provides a mode of counteracting the function of biomolecular condensates without condensate dissolution. Specifically, the negative regulator SLMAP forms Hippo-inactivating condensates to facilitate pathway inhibition by the STRIPAK complex. In response to cell-cell contact or osmotic stress, the positive regulators AMOT and KIBRA form Hippo-activating condensates to facilitate pathway activation. The functionally antagonizing SLMAP and AMOT/KIBRA condensates further coalesce into a common phase to inhibit STRIPAK function. These findings provide a paradigm for restricting the activity of biomolecular condensates without condensate dissolution, shed light on the molecular principles of multiphase organization, and offer a conceptual framework for understanding upstream regulation of the Hippo signaling pathway.

Original languageEnglish (US)
Pages (from-to)4376-4393.e18
JournalCell
Volume185
Issue number23
DOIs
StatePublished - Nov 10 2022

Keywords

  • AMOT
  • Hippo pathway
  • KIBRA
  • STRIPAK
  • YAP
  • biomolecular condensates
  • cell-cell contact
  • cytoskeleton
  • multiphase
  • osmotic stress

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Multiphase coalescence mediates Hippo pathway activation'. Together they form a unique fingerprint.

Cite this