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Updated: Aug 23, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Multiphase coalescence mediates Hippo pathway activation.

Li Wang1, Kyungsuk Choi1, Ting Su1

  • 1Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

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|November 1, 2022
PubMed
Summary

Scientists discovered a new way to control biomolecular condensates without dissolving them. This involves upstream regulators of the Hippo signaling pathway forming distinct condensates that merge to regulate cellular functions.

Keywords:
AMOTHippo pathwayKIBRASTRIPAKYAPbiomolecular condensatescell-cell contactcytoskeletonmultiphaseosmotic stress

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology
  • Signal Transduction

Background:

  • Biomolecular condensate function is often limited by dissolution.
  • Mechanisms to suppress condensate activity without dissolution remain largely unknown.
  • The Hippo signaling pathway plays a crucial role in cell growth and organ size.

Purpose of the Study:

  • To investigate if biomolecular condensate function can be suppressed without dissolution.
  • To elucidate the role of upstream regulators in modulating Hippo signaling pathway activity.
  • To understand the principles of multiphase organization in biological systems.

Main Methods:

  • Investigated the formation and interaction of condensates formed by SLMAP, AMOT, and KIBRA.
  • Utilized techniques to observe condensate coalescence and its effect on STRIPAK complex function.
  • Analyzed the upstream regulation of the Hippo signaling pathway under different cellular conditions.

Main Results:

  • Upstream regulators of the Hippo pathway form functionally antagonizing condensates.
  • SLMAP forms Hippo-inactivating condensates, while AMOT and KIBRA form Hippo-activating condensates.
  • Coalescence of these opposing condensates into a common phase inhibits STRIPAK complex function, suppressing pathway activity without dissolution.

Conclusions:

  • A novel paradigm for regulating biomolecular condensate activity without dissolution is presented.
  • Multiphase organization involving functionally antagonistic condensates provides a mechanism for fine-tuning cellular processes.
  • This study offers insights into the upstream regulation of the Hippo signaling pathway and condensate behavior.