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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
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The Spectrin cytoskeleton regulates the Hippo signalling pathway
Georgina C Fletcher1, Ahmed Elbediwy1, Ichha Khanal1
1Epithelial Biology Laboratory, Cancer Research UK - London Research Institute, London, UK.
The EMBO Journal
|February 26, 2015
Summary
Spectrin cytoskeleton regulates Hippo signaling in epithelial cells. Loss of Spectrin causes tissue overgrowth, while Spectrin
Area of Science:
- Cell biology
- Developmental biology
- Biochemistry
Background:
- The Spectrin cytoskeleton is polarized in epithelial cells, but its function is unclear.
- Hippo signaling is crucial for tissue growth and organ size control.
Purpose of the Study:
- To investigate the role of the Spectrin cytoskeleton in regulating Hippo signaling in epithelial cells.
- To identify the specific Spectrin isoforms and their localization involved in Hippo pathway regulation.
Main Methods:
- Genetic manipulation in Drosophila models (wing, eye, ovary, intestine).
- Immunofluorescence microscopy to assess protein localization.
- Analysis of Hippo target gene expression and YAP localization in human epithelial cells.
Main Results:
- Loss of apical Spectrins in Drosophila leads to tissue overgrowth and misregulation of Hippo target genes, mimicking loss of Crumbs (Crb) or Expanded (Ex).
- Apical Spectrin interacts with Expanded (Ex) at the apical membrane to inhibit Yki activity.
- Basolateral Spectrins, but not apical Spectrins, are essential for Yki repression in ovarian and intestinal epithelia.
- Spectrin cytoskeleton regulates YAP localization in human epithelial cells in response to cell density.
Conclusions:
- Spectrin cytoskeleton, both apical and basolateral, acts as a regulator of Hippo signaling.
- Spectrins are implicated as potential mechanosensors in epithelial cells.
- This study reveals a novel role for Spectrin in controlling tissue homeostasis and organ size.
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