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Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration.
Yu-Chiuan Chang1, Jhen-Wei Wu2, Yi-Chi Hsieh2
1Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, 1 University Rd., Tainan City 701, Taiwan, Republic of China; Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
Cell Reports
|February 22, 2018
Summary
The study reveals that Rap1 regulates collective cell migration polarity. Its hyperactivation or hypoactivation disrupts cell orientation and protrusion formation, highlighting its crucial role in group migration dynamics.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Collective cell migration is essential for development and disease, requiring coordinated cell polarity.
- The molecular mechanisms governing group polarity during migration remain incompletely understood.
- Drosophila border cells provide a tractable in vivo model for studying collective cell migration.
Purpose of the Study:
- To elucidate the molecular mechanisms controlling collective cell migration and group polarity.
- To investigate the role of Rap1 in regulating cell polarity and protrusion dynamics during collective migration.
- To identify genetic factors that modulate Rap1-dependent collective cell migration.
Main Methods:
- Forward genetic screen in Drosophila to identify genes affecting border cell migration.
- Analysis of cell polarity, actin network asymmetry, and protrusion formation.
- Investigating the interaction between Rap1 and the Hippo pathway.
Main Results:
- Rap1 activity is critical for establishing front/back polarity in migrating border cell clusters.
- Hyperactive Rap1 disrupts cluster polarity, leading to misoriented protrusions and loss of actin asymmetry.
- Hypoactive Rap1 results in reduced protrusions and "cluster spinning" during migration.
- Downregulation of Hippo pathway components (hpo, mats) exacerbates Rap1-V12-induced migration defects.
- Rap1 interacts with the Hippo kinase domain, suppressing its activity and promoting F-actin elongation.
Conclusions:
- Rap1 is a key regulator of collective cell migration polarity and protrusion formation.
- The Hippo pathway modulates Rap1's effect on collective cell migration.
- Understanding Rap1 and Hippo pathway interplay offers insights into collective cell migration control.
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