Morphogenic Effects of Ezrin Require a Phosphorylation-Induced Transition from Oligomers to Monomers at the Plasma Membrane

doi:10.1083/jcb.150.1.193

Published online 10 July 2000. doi:10.1083/jcb.150.1.193

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© The Rockefeller University Press, 0021-9525/2000//193 $5.00
The Journal of Cell Biology, Volume 150, Number 1, , 2000 193-204

Original Article

Morphogenic Effects of Ezrin Require a Phosphorylation-Induced Transition from Oligomers to Monomers at the Plasma Membrane

Alexis Gautreau^a, Daniel Louvard^a, and Monique Arpin^a

^a Laboratoire de Morphogénèse et Signalisation Cellulaires, UMR 144 CNRS/Institut Curie, 75248 Paris Cedex 05, France
Laboratoire de Morphogénèse et Signalisation Cellulaires, UMR 144 CNRS/Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.33 1 42 34 63 7733 1 42 34 63 72

marpin{at}curie.fr

ERM (ezrin, radixin, moesin) proteins act as linkers betweenthe plasma membrane and the actin cytoskeleton. An interactionbetween their NH₂- and COOH-terminal domains occurs intramolecularlyin closed monomers and intermolecularly in head-to-tail oligomers.In vitro, phosphorylation of a conserved threonine residue (T567in ezrin) in the COOH-terminal domain of ERM proteins disruptsthis interaction. Here, we have analyzed the role of this phosphorylationevent in vivo, by deriving stable clones producing wild-type,T567A, and T567D ezrin from LLC-PK1 epithelial cells. We foundthat T567A ezrin was poorly associated with the cytoskeleton,but was able to form oligomers. In contrast, T567D ezrin wasassociated with the cytoskeleton, but its distribution was shiftedfrom oligomers to monomers at the membrane. Moreover, productionof T567D ezrin induced the formation of lamellipodia, membraneruffles, and tufts of microvilli. Both T567A and T567D ezrinaffected the development of multicellular epithelial structures.Collectively, these results suggest that phosphorylation ofERM proteins on this conserved threonine regulates the transitionfrom membrane-bound oligomers to active monomers, which induceand are part of actin-rich membrane projections.

Key Words: ERM • head-to-tail interaction • conformation • actin • cytoskeleton

Abbreviations used in this paper: C-ERMAD, COOH-terminal ERMassociation domain; ERM, ezrin, radixin, moesin; N-ERMAD, NH₂-terminalERM association domain; wt, wild-type.

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