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A more recent version of this article appeared on May 1, 2003
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Submitted on July 18, 2002
Revised on December 4, 2002
Accepted on January 16, 2003
1 UMR 144 CNRS/Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
* Corresponding author. E-mail address: marpin{at}curie.fr.
Ezrin, a membrane cytoskeleton linker, is involved in cellular functions including epithelial cell morphogenesis and adhesion. A mutant form of ezrin, ezrin T567D, maintains the protein in an open conformation, which when expressed in MDCK cells causes extensive formation of lamellipodia and altered cell-cell contacts at low cell density. Furthermore, these cells do not form tubules when grown in a collagen type I matrix. While measuring the activity of Rho family GTPases, we found that Rac1, but not RhoA or Cdc 42, is activated in ezrin T567D expressing cells, compared to cells expressing wild type ezrin. Together with Rac1 activation, we observed an accumulation of E-cadherin in intracellular compartments and a concomitant decrease in the level of E-cadherin present at the plasma membrane. This effect could be reversed with a dominant negative form of Rac1, N17Rac1. We show that after a calcium switch, the delivery of E-cadherin from an internalized pool to the plasma membrane is greatly delayed in ezrin T567D producing cells. In confluent cells, ezrin T567D production decreases the rate of E-cadherin internalization. Our results identify a new role for ezrin in cell adhesion through the activation of the GTPase Rac1 and the trafficking of E-cadherin to the plasma membrane.
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