PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation

Area of Science:

• Cell Biology
• Biophysics

Background:

• Biomolecular condensates are increasingly recognized for their roles in cellular functions.
• While liquid-like condensates are well-studied, the function and regulation of solid-like condensates remain less understood.

Purpose of the Study:

• To investigate the role and regulation of solid-like biomolecular condensates in cellular physiology.
• To elucidate the mechanisms governing the formation and disassembly of Merlin-based solid condensates.

Main Methods:

• Localization studies of the tumor suppressor Merlin in *Drosophila* epithelia.
• Analysis of Merlin condensation, requiring phosphatidylinositol-4-phosphate (PI4P)-mediated membrane targeting.
• Investigation of regulatory mechanisms involving Pez and cytoskeletal tension.

Main Results:

• Merlin forms solid-like condensates at the medial apical cortex, activating Hippo signaling.
• Merlin condensation is dependent on PI4P and regulated by Pez and cytoskeletal tension.
• Solid-like material properties are essential for condensate function and stability.

Conclusions:

• Solid-like condensates play a vital role in normal physiology.
• Merlin-based solid condensates are regulated by specific molecular cues and physical forces.
• This work provides insights into the formation and disassembly mechanisms of solid biomolecular condensates.