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Acidosis Regulates Microtubule Dynamics via the β1 Integrin/RhoA/CRMP-2 Axis
Dariusz Lachowski1,2, Ernesto Cortes3, Vasyl Mykuliak4,5
1Department of Neuroscience and Biomedical Sciences, Universidad Carlos III de Madrid, Getafe, Madrid 28903, Spain.
Journal of the American Chemical Society
|May 20, 2026
Summary
Acidosis, or low extracellular pH, impacts microtubule stability by activating β1 integrin. This molecular pathway affects cell organization and offers potential drug targets for acidosis-related conditions.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Microtubules are crucial cytoskeletal components in eukaryotic cells.
- Previous studies on pH effects on microtubules focused on intracellular pH.
- The impact of extracellular pH on microtubule dynamics was not well understood.
Purpose of the Study:
- To investigate how extracellular pH influences microtubule stability.
- To elucidate the molecular mechanisms linking acidosis to changes in microtubule dynamics.
Main Methods:
- Investigated the effect of acidosis on β1 integrin activation.
- Analyzed the role of RhoA/ROCK signaling pathway.
- Examined the phosphorylation of Collapsin Response Mediator Protein-2 (CRMP-2).
- Assessed changes in Golgi apparatus positioning and architecture.
Main Results:
- Acidosis activates β1 integrin by increasing its affinity for ligands.
- Protonation of Asp138 in β1 integrin is key to this activation.
- This leads to RhoA/ROCK activation and CRMP-2 phosphorylation.
- Microtubule stability is negatively regulated, altering Golgi apparatus organization.
Conclusions:
- Extracellular pH significantly modulates microtubule dynamics through a defined mechanochemical pathway.
- This mechanism connects low extracellular pH to cellular organization, impacting processes like cell division and trafficking.
- Findings provide insights into acidosis-related cellular changes and potential therapeutic targets.
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