title: Ezrin regulates microvillus morphogenesis by promoting distinct activities of Eps8 proteins.
abstract: The mechanisms that regulate actin filament polymerization resulting in the morphogenesis of the brush border microvilli in epithelial cells remain unknown. Eps8, the prototype of a family of proteins capable of capping and bundling actin filaments, has been shown to bundle the microvillar actin filaments. We report that Eps8L1a, a member of the Eps8 family and a novel ezrin-interacting partner, controls microvillus length through its capping activity. Depletion of Eps8L1a leads to the formation of long microvilli, whereas its overexpression has the opposite effect. We demonstrate that ezrin differentially modulates the actin-capping and -bundling activities of Eps8 and Eps8L1a during microvillus assembly. Coexpression of ezrin with Eps8 promotes the formation of membrane ruffles and tufts of microvilli, whereas expression of ezrin and Eps8L1a induces the clustering of actin-containing structures at the cell surface. These distinct morphological changes are neither observed when a mutant of ezrin defective in its binding to Eps8/Eps8L1a is coexpressed with Eps8 or Eps8L1a nor observed when ezrin is expressed with mutants of Eps8 or Eps8L1a defective in the actin-bundling or -capping activities, respectively. Our data show a synergistic effect of ezrin and Eps8 proteins in the assembly and organization of actin microvillar filaments.
authors.affiliation: Unité Mixte de Recherche 144, Centre National de la Recherche Scientifique/Institut Curie, 75248 Paris, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zwaenepoel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Naba
authors.forename: Marcel Menezes Lyra
authors.initials: MM
authors.lastname: Da Cunha
authors.forename: Laurence
authors.initials: L
authors.lastname: Del Maestro
authors.forename: Etienne
authors.initials: E
authors.lastname: Formstecher
authors.forename: Daniel
authors.initials: D
authors.lastname: Louvard
authors.forename: Monique
authors.initials: M
authors.lastname: Arpin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D018374:LLC-PK1 Cells; D008871:Microvilli / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D034421:Sus scrofa; D013552:Swine; D000099149:Ezrin
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099149:Ezrin