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Inhibition of negative feedback for persistent epithelial cell-cell junction contraction by p21-activated kinase 3
Hiroyuki Uechi1,2, Kazuki Fukushima1, Ryota Shirasawa1
1Laboratory for Histogenetic Dynamics, Graduate School of Life Sciences, Tohoku University, 6-3, Aramaki-aza-aoba, Aoba-ku, Sendai, 980-8578, Japan.
Nature Communications
|June 20, 2022
Summary
Contractile forces regulate cell shape, but their absence disrupts cell-cell junction shortening. p21-activated kinase 3 (Pak3) normally prevents abnormal actin protrusions, ensuring proper cell junction contraction.
Area of Science:
- Cell Biology
- Mechanobiology
- Cytoskeletal Dynamics
Background:
- Actin-based mechanical forces drive cellular dynamics, including contraction and protrusion.
- Myosin II is crucial for contractile force generation at cell-cell junctions.
- Proper regulation of bidirectional forces is essential for cellular deformation and tissue integrity.
Purpose of the Study:
- To investigate the role of p21-activated kinase 3 (Pak3) in regulating cell-cell junction contraction.
- To elucidate the mechanisms by which contractile forces can perturb junction shortening.
- To understand how Pak3 facilitates persistent junction shortening.
Main Methods:
- Depletion of Pak3 in cells.
- Analysis of actin protrusions and myosin II localization at cell-cell junctions.
- Assessment of E-cadherin levels at adherens junctions.
- Functional assays of junction shortening.
- Rescue experiments by overexpressing E-cadherin.
Main Results:
- Pak3 depletion leads to abnormal actin protrusions at shortening junctions.
- Loss of Pak3 causes decreased E-cadherin at adherens junctions.
- Myosin II mislocalizes at junctions lacking Pak3, hindering shortening.
- E-cadherin overexpression rescues myosin II distribution and junction contraction.
- Contractility can both induce and perturb junction contraction.
Conclusions:
- Pak3 plays a critical role in preventing contractility-induced perturbations during cell-cell junction shortening.
- Pak3 facilitates persistent junction shortening by attenuating these perturbations.
- E-cadherin is essential for proper myosin II localization and junction contraction, and its levels are regulated by Pak3.
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