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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation
Takashi Ishiuchi1, Masatoshi Takeichi
1RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
Nature Cell Biology
|June 21, 2011
Summary
Willin and Par3 proteins control epithelial cell shape by regulating actomyosin cables. Their depletion causes apical constriction via Rho-associated kinases (ROCKs) and loss of aPKC, revealing a new pathway for epithelial morphogenesis.
Area of Science:
- Cell Biology
- Developmental Biology
- Epithelial Morphogenesis
Background:
- Epithelial morphogenesis relies on apical-domain constriction.
- Apical junctional complexes (AJCs) connect epithelial cells.
- Actomyosin cables at AJCs regulate contractility via Rho-associated kinases (ROCKs).
Purpose of the Study:
- To investigate the roles of Willin and Par3 in regulating ROCK-dependent apical constriction.
- To elucidate the molecular pathway controlling epithelial apical morphology.
Main Methods:
- Depletion of Willin and Par3 proteins.
- Analysis of aPKC and Par6 localization at AJCs.
- Quantification of ROCK levels at AJCs.
- Assessment of apical constriction and epithelial morphology.
Main Results:
- Willin recruits aPKC and Par6 to AJCs independently of Par3.
- Simultaneous depletion of Willin and Par3 removes aPKC and Par6, inducing apical constriction.
- This constriction results from increased AJC-associated ROCKs due to aPKC loss.
- aPKC phosphorylates ROCK, suppressing its junctional localization.
Conclusions:
- A novel Willin/Par3-aPKC-ROCK pathway regulates epithelial apical morphology.
- This pathway controls ROCK activity and localization to modulate apical constriction.
- Findings provide insights into the molecular mechanisms governing epithelial shape regulation.
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