Ezrin is an effector of hepatocyte growth factor-mediated migration and morphogenesis in epithelial cells

Tiziana Crepaldi, Alexis Gautreau, Paolo M. Comoglio, Daniel Louvard, Monique Arpin

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

The dissociation, migration, and remodeling of epithelial monolayers induced by hepatocyte growth factor (HGF) entail modifications in cell adhesion and in the actin cytoskeleton through unknown mechanisms. Here we report that ezrin, a membrane-cytoskeleton linker, is crucial to HGF-mediated morphogenesis in a polarized kidney-derived epithelial cell line, LLC-PK1. Ezrin is a substrate for the tyrosine kinase HGF receptor both in vitro and in vivo. HGF stimulation causes enrichment of ezrin recovered in the detergent-insoluble cytoskeleton fraction. Overproduction of wild-type ezrin, by stable transfection in LLC-PK1 cells, enhances cell migration and tubulogenesis induced by HGF stimulation. Overproduction of a truncated variant of ezrin causes mislocalization of endogenous ezrin from microvilli into lateral surfaces. This is concomitant with altered cell shape, characterized by loss of microvilli and cell flattening. Moreover, the truncated variant of ezrin impairs the morphogenic and motogenic response to HGF, thus suggesting a dominant-negative mechanism of action. Site-directed mutagenesis of ezrin codons Y145 and Y353 to phenylalanine does not affect the localization of ezrin at microvilli, but perturbs the motogenic and morphogenic responses to HGF. These results provide evidence that ezrin displays activities that can control cell shape and signaling.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalJournal of Cell Biology
Volume138
Issue number2
DOIs
Publication statusPublished - Jul 28 1997

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Hepatocyte Growth Factor
Morphogenesis
Epithelial Cells
Microvilli
Cell Shape
Cytoskeleton
ezrin
LLC-PK1 Cells
Proto-Oncogene Proteins c-met
Site-Directed Mutagenesis
Phenylalanine
Actin Cytoskeleton
Cell Adhesion
Codon
Detergents
Protein-Tyrosine Kinases
Cell Movement
Transfection
Kidney
Cell Line

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ezrin is an effector of hepatocyte growth factor-mediated migration and morphogenesis in epithelial cells. / Crepaldi, Tiziana; Gautreau, Alexis; Comoglio, Paolo M.; Louvard, Daniel; Arpin, Monique.

In: Journal of Cell Biology, Vol. 138, No. 2, 28.07.1997, p. 423-434.

Research output: Contribution to journalArticle

Crepaldi, Tiziana ; Gautreau, Alexis ; Comoglio, Paolo M. ; Louvard, Daniel ; Arpin, Monique. / Ezrin is an effector of hepatocyte growth factor-mediated migration and morphogenesis in epithelial cells. In: Journal of Cell Biology. 1997 ; Vol. 138, No. 2. pp. 423-434.
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