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Dissecting Mechanoenzymatic Properties of Processive Myosins with Ultrafast Force-Clamp Spectroscopy
Published on: July 1, 2021
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A biochemical network controlling basal myosin oscillation.
Xiang Qin1,2,3, Edouard Hannezo4,5, Thomas Mangeat1,2
1Université de Toulouse, UPS, F-31062, Toulouse, France.
Nature Communications
|March 25, 2018
Summary
Epithelial cells exhibit myosin II oscillations driven by a biochemical loop of ROCK and myosin phosphatase, not cortical tension. This discovery reveals an intrinsic oscillator regulating cell force generation.
Area of Science:
- Cell Biology
- Biophysics
- Developmental Biology
Background:
- The actomyosin cytoskeleton generates cellular tension and exhibits spontaneous oscillations in various biological systems.
- While signaling pathways regulating myosin activity are known, the precise origin of these oscillatory behaviors remains elusive.
- Epithelial cells utilize actomyosin networks for mechanical integrity and force generation.
Purpose of the Study:
- To elucidate the underlying mechanism driving basal myosin II oscillations in the Drosophila ovarian epithelium.
- To determine whether actomyosin cortical tension or a biochemical oscillator governs myosin II dynamics.
- To identify the key molecular players and regulatory loops involved in myosin II oscillation.
Main Methods:
- Utilized Drosophila genetics to manipulate key regulatory proteins.
- Employed live imaging techniques to visualize cytoskeletal dynamics in real-time.
- Integrated computational modeling and optogenetics to probe the biochemical oscillator.
Main Results:
- Demonstrated that myosin II oscillations are regulated by a biochemical oscillator involving ROCK (Rho-associated protein kinase) and myosin phosphatase, independent of actomyosin cortical tension.
- Identified a diffusive ROCK flow, crucial for linking junctional Rho1 to the actomyosin cortex, maintained by a ROCK kinase activity self-activation loop.
- Observed local enrichment of myosin phosphatase, which subsequently inhibits ROCK and myosin II signaling, creating a feedback loop.
Conclusions:
- Uncovered an intrinsic biochemical oscillator within the myosin II regulatory network as the source of oscillations in Drosophila ovarian epithelium.
- This oscillator, driven by ROCK and myosin phosphatase dynamics, governs the spatio-temporal regulation of force generation in epithelial cells.
- Provides fundamental insights into the mechanisms controlling cellular contractility and tissue morphogenesis.
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