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Adherens junction regulates cryptic lamellipodia formation for epithelial cell migration
Masayuki Ozawa1, Sylvain Hiver1, Takaki Yamamoto2
1Laboratory for Cell Adhesion and Tissue Patterning, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
The Journal of Cell Biology
|September 5, 2020
Summary
Adherens junctions (AJs) support cryptic lamellipodia (c-lamellipodia) formation in epithelial cells. This process, regulated by WAVE and Arp2/3 complexes, is crucial for ordered collective cell migration.
Area of Science:
- Cell Biology
- Biophysics
- Cancer Research
Background:
- Collective cell migration is vital for development and disease, including cancer invasion.
- Epithelial sheets utilize leader and follower cells, with followers forming cryptic lamellipodia (c-lamellipodia) at cell boundaries.
- Understanding c-lamellipodia formation is key to deciphering ordered epithelial sheet movement.
Purpose of the Study:
- To investigate the formation mechanism of c-lamellipodia in epithelial cells.
- To identify the molecular players and regulatory factors involved in c-lamellipodia generation.
- To elucidate the role of adherens junctions (AJs) in supporting collective cell migration.
Main Methods:
- Utilized adenocarcinoma-derived epithelial cells for experimental observations.
- Investigated the localization and function of WAVE and Arp2/3 complexes at AJs.
- Disrupted AJs by removing αE-catenin to observe effects on c-lamellipodia formation and cell migration.
- Analyzed the role of myosin II activation and actomyosin contractility in c-lamellipodia dynamics.
- Assessed the influence of mechanical junctional properties on c-lamellipodia growth.
Main Results:
- C-lamellipodia were observed to form sporadically around E-cadherin-based adherens junctions (AJs).
- WAVE and Arp2/3 complexes localized to AJs and were essential for c-lamellipodia formation and follower cell trailing.
- Disruption of AJs led to uncontrolled c-lamellipodia growth, driven by myosin II activation and actomyosin contraction.
- C-lamellipodia formation was favored at mechanically weaker sites within the AJs.
Conclusions:
- Adherens junctions (AJs) are not only structural components but also regulatory hubs for c-lamellipodia formation.
- The recruitment of actin regulators like WAVE and Arp2/3 complexes at AJs is critical for ordered collective migration.
- Mechanical properties of AJs influence c-lamellipodia dynamics, contributing to coordinated epithelial cell movement.
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