An apical MRCK-driven morphogenetic pathway controls epithelial polarity
Ceniz Zihni1, Evi Vlassaks2, Stephen Terry1
1Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK.
Nature Cell Biology
|August 22, 2017
Summary
Myotonic dystrophy-related Cdc42-binding kinase (MRCK) activates apical actomyosin contractility, segregating polarity proteins and driving epithelial morphogenesis. This establishes an apical origin for cytoskeletal reorganization coupled with polarity signaling.
Area of Science:
- Cell Biology
- Developmental Biology
- Epithelial Biology
Background:
- Polarized epithelia establish distinct apical and basolateral membrane domains crucial for tissue function.
- Cell polarization is regulated by polarity determinants, including the evolutionarily conserved partitioning-defective (PAR) proteins.
- PAR protein segregation is hypothesized to result from asymmetric actomyosin contractions, but the activation mechanism remains unclear.
Purpose of the Study:
- To elucidate the mechanism of activation of apically polarized actomyosin contractility.
- To identify the upstream regulators of apical actomyosin contractility and their role in cell polarization and morphogenesis.
- To understand how cytoskeletal reorganization is coupled to PAR polarity signaling.
Main Methods:
- Investigated the role of the Cdc42 effector Myotonic dystrophy-related Cdc42-binding kinase (MRCK) in epithelial cell polarization.
- Utilized techniques to analyze actomyosin contractility, protein segregation, and cytoskeletal organization in polarized epithelia.
- Examined the function of MRCK-activated contractility in apical differentiation and morphogenesis in vertebrate epithelia and Drosophila photoreceptors.
Main Results:
- MRCK activates myosin-II at the apical pole, leading to the segregation of aPKC-Par6 from junctional Par3 and defining the apical domain.
- Apically polarized MRCK-activated actomyosin contractility is reinforced by cooperation with aPKC-Par6, which downregulates antagonistic RhoA-driven junctional contractility.
- This apical contractility drives the polarization of cytosolic brush border determinants and promotes apical morphogenesis.
Conclusions:
- MRCK-activated polarized actomyosin contractility is essential for apical differentiation and morphogenesis in various epithelial systems.
- This study reveals an apical origin of actomyosin-driven morphogenesis, linking cytoskeletal dynamics to PAR polarity signaling.
- The findings provide a novel mechanism for how apical cell surface domains are established and maintained.
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