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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Actin cytoskeleton regulates Hippo signaling
Pradeep Reddy1, Masashi Deguchi, Yuan Cheng
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
Plos One
|September 17, 2013
Summary
The actin cytoskeleton regulates organ size by influencing the Hippo pathway. Stabilizing actin with jasplakinolide activates YAP, a key molecule, and increases downstream growth factors.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The Hippo pathway is crucial for controlling organ size by regulating cell proliferation and apoptosis.
- The precise mechanisms by which the actin cytoskeleton influences Hippo signaling remain incompletely understood.
Purpose of the Study:
- To investigate the role of the actin cytoskeleton as an upstream regulator of the Hippo signaling pathway.
- To determine if manipulating actin dynamics affects YAP activation and downstream gene expression.
Main Methods:
- Elevated filamentous (F)-actin levels in HeLa cells using the actin-stabilizing drug jasplakinolide.
- Assessed YAP phosphorylation and nuclear localization.
- Quantified the expression of downstream CCN growth factors (CCN1/CYR61 and CCN2/CTGF).
- Utilized YAP "knock-down" cells to confirm YAP's role in the observed effects.
Main Results:
- Induction of F-actin formation led to decreased YAP phosphorylation, indicating YAP activation.
- Activated YAP translocated to the cell nucleus.
- Increased YAP levels correlated with elevated expression of CCN1/CYR61 and CCN2/CTGF.
- The effects of actin stabilization on YAP and CCN factors were abrogated in YAP "knock-down" cells.
Conclusions:
- The actin cytoskeleton acts as an upstream regulator of the Hippo signaling pathway.
- Actin stabilization can activate YAP, leading to increased expression of downstream CCN growth factors.
- These findings elucidate a novel regulatory mechanism controlling organ size and cellular growth.
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