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Mechanosensing Controlled Directly by Tyrosine Kinases
Bo Yang1, Zi Zhao Lieu1, Haguy Wolfenson2
1Mechanobiology Institute, National University of Singapore , Singapore 117411.
Nano Letters
|August 26, 2016
Summary
Receptor tyrosine kinases AXL and ROR2 control cell mechanics by directly regulating local contractions. This discovery sheds light on how cells sense matrix rigidity and form tissues.
Area of Science:
- Cell Biology
- Biochemistry
- Biophysics
Background:
- Cellular mechanics are crucial for tissue formation.
- Tyrosine kinases play a role in controlling cell mechanics.
- Cells sense matrix rigidity through local contractions.
Purpose of the Study:
- To investigate the role of receptor tyrosine kinases (RTKs) AXL and ROR2 in cell mechanics and rigidity sensing.
- To understand how RTKs influence local cellular contractions.
Main Methods:
- Knockdown of RTKs AXL and ROR2.
- Analysis of cell contraction events and matrix rigidity sensing.
- Molecular localization and binding assays for phospho-AXL, ROR2, tropomyosin 2.1, myosin IIA, and filamin A.
Main Results:
- Knocking down AXL and ROR2 altered rigidity sensing.
- AXL and ROR2 depletion increased the magnitude or duration of local contractions.
- Phospho-AXL and ROR2 were found in contraction units, binding key contractile proteins.
- Phosphorylated AXL directly phosphorylates tropomyosin, impacting adhesion formation.
Conclusions:
- AXL and ROR2 directly regulate local mechanosensory contractions.
- These RTKs influence morphogenic processes by controlling cell mechanics.
- Ligand binding is not required for ROR2 function in this context.
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