YAP regulates cell mechanics by controlling focal adhesion assembly

Area of Science:

• Cell Biology
• Mechanobiology
• Biochemistry

Background:

• Hippo pathway effectors YAP/TAZ function as critical mechanosensors.
• Their activity is regulated by the extracellular matrix (ECM) and focal adhesions (FAs).
• A hierarchical model suggests Hippo pathway elements are controlled by FAs.

Purpose of the Study:

• To elucidate the molecular mechanism linking cell spreading and RhoA GTPase activity to YAP-mediated focal adhesion formation.
• To understand how YAP stabilizes actin cytoskeleton anchorage to the cell membrane.
• To investigate the role of YAP's transcriptional activity in regulating cell mechanics and behavior.

Main Methods:

• Investigated the molecular interplay between cell spreading, RhoA GTPase, and focal adhesion dynamics.
• Utilized YAP's co-transcriptional function to identify downstream gene targets.
• Assessed the impact of modulating YAP transcriptional activity on cellular mechanics, adhesion, and morphology.

Main Results:

• Unveiled a mechanism where cell spreading and RhoA GTPase activity promote FA formation through YAP.
• Demonstrated that YAP's transcriptional activity, involving integrins and FA proteins, stabilizes cytoskeletal anchorage.
• Showed that tuning YAP activity alters cell mechanics, adhesion strength, shape, migration, and differentiation.

Conclusions:

• YAP acts as a key determinant of cell mechanics in response to ECM cues.
• YAP's mechanosensing activity is intrinsically linked to its transcriptional function.
• This study provides novel insights into YAP's role in integrating mechanical signals for cellular regulation.