Cortical tension regulates desmosomal morphogenesis
Marcin Moch1, Jana Schieren1, Rudolf E Leube1
1Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany.
Frontiers in Cell and Developmental Biology
|October 21, 2022
Summary
Mechanical stress impacts epithelial cell junctions. Reduced actomyosin activity decreases desmosomal protein turnover, suggesting desmosomes sense and respond to mechanical forces.
Area of Science:
- Cell biology
- Biophysics
- Epithelial biology
Background:
- Epithelial mechanical stability relies on cell-cell adhesion and cytoskeletal integration.
- The interplay between actomyosin and desmosome-keratin systems regulates epithelial mechanics.
- The role of desmosomes in mechanical force sensing remains largely unexplored.
Purpose of the Study:
- To investigate how mechanical stress affects desmosome plasticity and protein turnover.
- To explore the desmosome-keratin scaffold's role in force sensing.
Main Methods:
- Inactivation of the actomyosin system in human keratinocytes (HaCaT) and canine kidney cells (MDCK) using inhibitors like para-nitro-blebbistatin, latrunculin B, and Y-27632.
- Monitoring changes in desmosomal protein turnover and cell elastic modulus.
Main Results:
- Partial inhibition of myosin II decreased cell elastic modulus and desmosomal protein turnover, particularly for desmoplakin I (DspI) and desmoglein 2 (Dsg2).
- Desmocollin 2 (Dsc2) and E-cadherin turnover remained unaffected.
- Inhibition of actin polymerization and ROCK-driven contractility also reduced DspI turnover.
Conclusions:
- Altered cortical force balance affects desmosome formation, growth, and composition.
- Desmosomes exhibit differential protein turnover in response to mechanical changes.
- Evidence suggests a novel desmosomal mechanosensing and mechanoresponse pathway exists.
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