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Updated: Jun 2, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila
Beatriz García Fernández1, Pedro Gaspar, Catarina Brás-Pereira
1Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, P-2780-156 Oeiras, Portugal.
Abstract:
The conserved Hippo tumor suppressor pathway is a key kinase cascade that controls tissue growth by regulating the nuclear import and activity of the transcription co-activator Yorkie. Here, we report that the actin-Capping Protein αβ heterodimer, which regulates actin polymerization, also functions to suppress inappropriate tissue growth by inhibiting Yorkie activity. Loss of Capping Protein activity results in abnormal accumulation of apical F-actin, reduced Hippo pathway activity and the ectopic expression of several Yorkie target genes that promote cell survival and proliferation. Reduction of two other actin-regulatory proteins, Cofilin and the cyclase-associated protein Capulet, cause abnormal F-actin accumulation, but only the loss of Capulet, like that of Capping Protein, induces ectopic Yorkie activity. Interestingly, F-actin also accumulates abnormally when Hippo pathway activity is reduced or abolished, independently of Yorkie activity, whereas overexpression of the Hippo pathway component expanded can partially reverse the abnormal accumulation of F-actin in cells depleted for Capping Protein. Taken together, these findings indicate a novel interplay between Hippo pathway activity and actin filament dynamics that is essential for normal growth control.
Insights
The actin-Capping Protein suppresses tissue growth by inhibiting Yorkie. Its loss causes abnormal F-actin accumulation and ectopic Yorkie activity, revealing a link between actin dynamics and Hippo pathway growth control.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- The Hippo pathway is a critical regulator of tissue growth and organ size.
- Yorkie is a transcription co-activator regulated by the Hippo pathway.
- Actin dynamics play roles in various cellular processes, including cell shape and motility.
Purpose of the Study:
- To investigate the role of actin-Capping Protein in regulating tissue growth.
- To explore the relationship between actin dynamics and the Hippo pathway.
- To understand how actin-regulatory proteins influence Yorkie activity.
Main Methods:
- Genetic manipulation of actin-regulatory proteins (Capping Protein, Cofilin, Capulet) in Drosophila.
- Analysis of F-actin accumulation using fluorescent imaging.
- Assessment of Hippo pathway activity and Yorkie target gene expression.
- Overexpression studies of Hippo pathway components.
Main Results:
- Loss of Capping Protein leads to abnormal F-actin accumulation and reduced Hippo pathway activity.
- Capping Protein and Capulet, but not Cofilin, suppress ectopic Yorkie activity.
- Abnormal F-actin accumulation occurs independently of Yorkie when Hippo activity is reduced.
- Overexpression of Expanded partially rescues F-actin defects in Capping Protein-depleted cells.
Conclusions:
- Actin-Capping Protein is a novel suppressor of tissue growth by inhibiting Yorkie.
- A new interplay exists between Hippo pathway signaling and actin filament dynamics.
- This interaction is crucial for maintaining normal tissue growth control.
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