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Confined migration: Microtubules control the cell rear
Manuel Thery1, Anna Akhmanova2
1CytoMorpho Lab, LPCV, UMR5168, Université Grenoble-Alpes, CEA/INRA/CNRS, Interdisciplinary Research Institute of Grenoble, 17 rue des Martyrs, 38054 Grenoble, France; CytoMorpho Lab, CBI, UMR8132, Université Paris Sciences et Lettres, Ecole Supérieure de Physique et Chimie Industrielles de la Ville de Paris, CEA/CNRS, Institut Pierre Gilles De Gennes, 6 rue Jean Calvin, 75005 Paris, France.
Current Biology : CB
|August 6, 2024
Summary
Cell migration in 3D environments depends on actin and microtubules. CLASP stabilizes microtubules at the cell rear, controlling contractility for nuclear movement through constrictions.
Area of Science:
- Cell biology
- Cytoskeleton dynamics
- Mechanobiology
Background:
- Cell migration through complex three-dimensional (3D) matrices is crucial for development and disease.
- The cytoskeleton, particularly actin filaments and microtubules, plays a vital role in cell motility.
- Understanding how cells navigate confined spaces is essential for regenerative medicine and cancer metastasis research.
Purpose of the Study:
- To investigate the role of microtubule stabilization at the cell rear during migration through narrow constrictions.
- To elucidate the interplay between microtubule dynamics, actomyosin contractility, and nuclear translocation in confined environments.
Main Methods:
- Live-cell imaging of migrating cells in 3D microfluidic devices.
- Fluorescent reporters for actin, microtubules, and contractility.
- Genetic manipulation to modulate CLASP and microtubule stability.
Main Results:
- Microtubule stabilization at the cell rear, dependent on CLASP, is critical for navigating constrictions.
- CLASP-mediated microtubule stabilization regulates actomyosin contractility.
- This regulation facilitates nuclear translocation and maintains cell integrity during passage through narrow spaces.
Conclusions:
- CLASP-dependent microtubule stabilization is a key mechanism controlling cell migration through confined 3D environments.
- The findings reveal a novel regulatory axis linking microtubule dynamics to actomyosin contractility for nuclear passage.
- This pathway is essential for preserving cell integrity during migration in complex terrains.
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