YAP condensates are highly organized hubs.

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Yes-associated protein (YAP)/TEAD signaling is vital for development, cell growth, and cancer.
• The precise mechanisms by which YAP, a transcriptional coactivator, activates target genes are not fully understood.
• While YAP is known to form condensates under osmotic stress to activate genes, its behavior under other stimuli and the general function of these condensates remain unclear.

Purpose of the Study:

• To investigate the formation, organization, and function of YAP condensates under different signaling conditions.
• To elucidate the role of YAP condensates in regulating YAP/TEAD target gene expression.
• To explore the molecular players involved in YAP condensate formation and stabilization.

Main Methods:

• Investigated endogenous YAP condensate formation in response to Hippo pathway signals and actin cytoskeletal tension.
• Utilized techniques to identify stabilizing factors and recruited coactivators within YAP condensates.
• Employed single-particle tracking to analyze YAP diffusion dynamics within condensates.

Main Results:

• Endogenous YAP forms sub-micron scale condensates regulated by the Hippo pathway and cytoskeletal tension.
• YAP condensate formation is stabilized by the transcription factor TEAD1 and recruits the coactivator BRD4.
• Single-particle tracking revealed that YAP diffusion is reduced within condensates, potentially enhancing target gene searching.

Conclusions:

• YAP condensate formation is a tightly regulated process crucial for YAP/TEAD-mediated gene expression.
• These condensates play a significant role in concentrating transcription factors and facilitating target gene activation.
• The findings provide new insights into the molecular mechanisms underlying YAP/TEAD signaling in biological processes and disease.