Dynamic actin remodeling during epithelial–mesenchymal transition depends on increased moesin expression
| Autor: | Diane L. Barber, Nikki Madson, Torsten Wittmann, Jennifer Haynes, Jyoti Srivastava |
|---|---|
| Přispěvatelé: | Nusrat, Asma |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Epithelial-Mesenchymal Transition
Myosin Light Chains 1.1 Normal biological development and functioning Moesin Actin filament organization Arp2/3 complex macromolecular substances Biology Microfilament Medical and Health Sciences Cell Line 03 medical and health sciences Actin remodeling of neurons Mice 0302 clinical medicine Underpinning research Transforming Growth Factor beta 2.1 Biological and endogenous factors Animals Humans Aetiology Phosphorylation Molecular Biology 030304 developmental biology 0303 health sciences Microfilament Proteins Actin remodeling Cell Biology Articles Biological Sciences Actin cytoskeleton Actins Cell biology Actin Cytoskeleton Hyaluronan Receptors Gene Expression Regulation Cell Biology of Disease 030220 oncology & carcinogenesis Focal Adhesion Protein-Tyrosine Kinases biology.protein Female MDia1 Developmental Biology |
| Zdroj: | Molecular Biology of the Cell Molecular biology of the cell, vol 22, iss 24 |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | LifeAct-GFP, a fluorescent reporter for actin filaments, is used to uncover the dynamics of actin cytoskeleton remodeling in real time during TGF-β–induced EMT. Efficient actin filament remodeling and complete transition to a mesenchymal phenotype depend on an increase in expression of the ERM protein moesin. Remodeling of actin filaments is necessary for epithelial–mesenchymal transition (EMT); however, understanding of how this is regulated in real time is limited. We used an actin filament reporter and high-resolution live-cell imaging to analyze the regulated dynamics of actin filaments during transforming growth factor-β–induced EMT of mammary epithelial cells. Progressive changes in cell morphology were accompanied by reorganization of actin filaments from thin cortical bundles in epithelial cells to thick, parallel, contractile bundles that disassembled more slowly but remained dynamic in transdifferentiated cells. We show that efficient actin filament remodeling during EMT depends on increased expression of the ezrin/radixin/moesin (ERM) protein moesin. Cells suppressed for moesin expression by short hairpin RNA had fewer, thinner, and less stable actin bundles, incomplete morphological transition, and decreased invasive capacity. These cells also had less α-smooth muscle actin and phosphorylated myosin light chain in cortical patches, decreased abundance of the adhesion receptor CD44 at membrane protrusions, and attenuated autophosphorylation of focal adhesion kinase. Our findings suggest that increased moesin expression promotes EMT by regulating adhesion and contractile elements for changes in actin filament organization. We propose that the transciptional program driving EMT controls progressive remodeling of actin filament architectures. |
| Databáze: | OpenAIRE |
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