Journal article
Essential functions of ezrin in maintenance of cell shape and lamellipodial extension in normal and transformed fibroblasts
Current biology, Vol.7(9), pp.682-688
09/01/1997
DOI: 10.1016/S0960-9822(06)00295-8
PMID: 9285722
Abstract
Background: Changes in cell shape and motility are important manifestations of oncogenic transformation, but the mechanisms underlying these changes and key effector molecules in the cytoskeleton remain unknown. The Fos oncogene induces expression of ezrin, the founder member of the ezrin/radixin/moesin (ERM) protein family, but not expression of the related ERM proteins, suggesting that ezrin has a distinct role in cell transformation. ERM proteins have been suggested to link the plasma membrane to the actin-based cytoskeleton and are substrates and anchoring sites for a variety of protein kinases. Here, we examined the role of ezrin in cellular transformation.
Results: Fos-mediated transformation of Rat-1 fibroblasts resulted in an increased expression and hyperphosphorylation of ezrin, and a concomitant increased association of ezrin with the cortical cytoskeleton. We tagged ezrin with green fluorescent protein and examined its distribution in normal and Fos-transformed fibroblasts: ezrin was concentrated at the leading edge of extending pseudopodia of Fos-transformed Rat-1 cells, and was mainly cytosolic in normal Rat-1 cells. Functional ablation of ezrin by micro-CALI (chromophore-assisted laser inactivation) blocked plasma-membrane ruffling and motility of Fos-transformed fibroblasts. Ablation of ezrin in normal Rat-1 cells caused a marked collapse of the leading edge of the cell.
Conclusions: Ezrin plays an important role in pseudopodial extension in Fos-transformed Rat-1 fibroblasts, and maintains cell shape in normal Rat-1 cells. The increased expression, hyperphosphorylation and subcellular redistribution of ezrin upon fibroblast transformation coupled with its roles in cell shape and motility suggest a critical role for ezrin in oncogenic transformation.
Details
- Title: Subtitle
- Essential functions of ezrin in maintenance of cell shape and lamellipodial extension in normal and transformed fibroblasts
- Creators
- Richard F Lamb - Beatson Institute for Cancer Research, CRC Beatson Laboratories, Wolfson Laboratory for Molecular Pathology, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UKBradford W Ozanne - Beatson Institute for Cancer Research, CRC Beatson Laboratories, Wolfson Laboratory for Molecular Pathology, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UKChristian Roy - Dynamique Moleculaire des Interactions Membranaires, CNRS UMR 5539, Universite Montpellier 2, CC 107, 34095 Montpellier, Cedex 5, FranceLynn McGarry - Beatson Institute for Cancer Research, CRC Beatson Laboratories, Wolfson Laboratory for Molecular Pathology, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UKChristopher Stipp - Department of Molecular and Cellular Biology, 16 Divinity Avenue, Harvard University, Cambridge, Massachusetts 02138, USAPaul Mangeat - Dynamique Moleculaire des Interactions Membranaires, CNRS UMR 5539, Universite Montpellier 2, CC 107, 34095 Montpellier, Cedex 5, FranceDaniel G Jay - Department of Molecular and Cellular Biology, 16 Divinity Avenue, Harvard University, Cambridge, Massachusetts 02138, USA
- Resource Type
- Journal article
- Publication Details
- Current biology, Vol.7(9), pp.682-688
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S0960-9822(06)00295-8
- PMID
- 9285722
- ISSN
- 0960-9822
- eISSN
- 1879-0445
- Language
- English
- Date published
- 09/01/1997
- Academic Unit
- Molecular Physiology and Biophysics; Biology
- Record Identifier
- 9984217421402771
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