Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1993 Jan 1; 120(1): 129–139.
PMCID: PMC2119498

Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker


Ezrin, a widespread protein present in actin-containing cell-surface structures, is a substrate of some protein tyrosine kinases. Based on its primary and secondary structure similarities with talin and band 4.1 it has been suggested that this protein could play a role in linking the cytoskeleton to the plasma membrane (Gould, K.L., A. Bretscher, F.S. Esch, and T. Hunter. 1989. EMBO (Eur. Mol. Biol. Organ.), J. 8:4133-4142; Turunen, O., R. Winqvist, R. Pakkanen, K.-H. Grzeschik, T. Wahlstrom, and A. Vaheri. 1989. J. Biol. Chem. 264:16727- 16732). To test this hypothesis, we transiently expressed the complete human ezrin cDNA, or truncated cDNAs encoding the amino- and carboxy- terminal domains of the protein, in CV-1 cells. Protein epitope tagging was used to unambiguously determine the subcellular distribution of the protein encoded by the transfected cDNA. We show that this protein is concentrated underneath the dorsal plasma membrane in all actin- containing structures and is partially detergent insoluble. The amino- terminal domain displays the same localization but is readily extractable by nonionic detergent. The carboxy-terminal domain colocalizes with microvillar actin filaments as well as with stress fibers and remains associated with actin filaments after detergent extraction, and with disorganized actin structures after cytochalasin D treatment. Our results clearly demonstrate that ezrin interacts with membrane-associated components via its amino-terminal domain, and with the cytoskeleton via its carboxy-terminal domain. The amino-terminal domain could include the main determinant that restricts the entire protein to the cortical cytoskeleton in contact with the dorsal plasma membrane and its specialized microdomains such as microvilli, microspikes and lamellipodia.

Full Text

The Full Text of this article is available as a PDF (4.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anderson RA, Lovrien RE. Glycophorin is linked by band 4.1 protein to the human erythrocyte membrane skeleton. Nature. 1984 Feb 16;307(5952):655–658. [PubMed]
  • Bretscher A. Purification of an 80,000-dalton protein that is a component of the isolated microvillus cytoskeleton, and its localization in nonmuscle cells. J Cell Biol. 1983 Aug;97(2):425–432. [PMC free article] [PubMed]
  • Bretscher A. Rapid phosphorylation and reorganization of ezrin and spectrin accompany morphological changes induced in A-431 cells by epidermal growth factor. J Cell Biol. 1989 Mar;108(3):921–930. [PMC free article] [PubMed]
  • Bretscher A. Microfilament structure and function in the cortical cytoskeleton. Annu Rev Cell Biol. 1991;7:337–374. [PubMed]
  • Burridge K, Connell L. A new protein of adhesion plaques and ruffling membranes. J Cell Biol. 1983 Aug;97(2):359–367. [PMC free article] [PubMed]
  • Burridge K, Mangeat P. An interaction between vinculin and talin. Nature. 1984 Apr 19;308(5961):744–746. [PubMed]
  • Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. [PMC free article] [PubMed]
  • Conboy J, Kan YW, Shohet SB, Mohandas N. Molecular cloning of protein 4.1, a major structural element of the human erythrocyte membrane skeleton. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9512–9516. [PMC free article] [PubMed]
  • Correas I, Leto TL, Speicher DW, Marchesi VT. Identification of the functional site of erythrocyte protein 4.1 involved in spectrin-actin associations. J Biol Chem. 1986 Mar 5;261(7):3310–3315. [PubMed]
  • Coudrier E, Reggio H, Louvard D. Characterization of an integral membrane glycoprotein associated with the microfilaments of pig intestinal microvilli. EMBO J. 1983;2(3):469–475. [PMC free article] [PubMed]
  • Everett AW, Nichol KA. Ezrin immunoreactivity in neuron subpopulations: cellular distribution in relation to cytoskeletal proteins in sensory neurons. J Histochem Cytochem. 1990 Aug;38(8):1137–1144. [PubMed]
  • Finidori J, Friederich E, Kwiatkowski DJ, Louvard D. In vivo analysis of functional domains from villin and gelsolin. J Cell Biol. 1992 Mar;116(5):1145–1155. [PMC free article] [PubMed]
  • Friederich E, Huet C, Arpin M, Louvard D. Villin induces microvilli growth and actin redistribution in transfected fibroblasts. Cell. 1989 Nov 3;59(3):461–475. [PubMed]
  • Frosch PM, Frosch M, Pfister T, Schaad V, Bitter-Suermann D. Cloning and characterisation of an immunodominant major surface antigen of Echinococcus multilocularis. Mol Biochem Parasitol. 1991 Oct;48(2):121–130. [PubMed]
  • Funayama N, Nagafuchi A, Sato N, Tsukita S, Tsukita S. Radixin is a novel member of the band 4.1 family. J Cell Biol. 1991 Nov;115(4):1039–1048. [PMC free article] [PubMed]
  • Gould KL, Cooper JA, Bretscher A, Hunter T. The protein-tyrosine kinase substrate, p81, is homologous to a chicken microvillar core protein. J Cell Biol. 1986 Feb;102(2):660–669. [PMC free article] [PubMed]
  • Gould KL, Bretscher A, Esch FS, Hunter T. cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. EMBO J. 1989 Dec 20;8(13):4133–4142. [PMC free article] [PubMed]
  • Hanzel D, Reggio H, Bretscher A, Forte JG, Mangeat P. The secretion-stimulated 80K phosphoprotein of parietal cells is ezrin, and has properties of a membrane cytoskeletal linker in the induced apical microvilli. EMBO J. 1991 Sep;10(9):2363–2373. [PMC free article] [PubMed]
  • Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K. Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage. Nature. 1986 Apr 10;320(6062):531–533. [PubMed]
  • Hunter T, Cooper JA. Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells. Cell. 1981 Jun;24(3):741–752. [PubMed]
  • Kreis TE. Microinjected antibodies against the cytoplasmic domain of vesicular stomatitis virus glycoprotein block its transport to the cell surface. EMBO J. 1986 May;5(5):931–941. [PMC free article] [PubMed]
  • Kreis TE. Microtubules containing detyrosinated tubulin are less dynamic. EMBO J. 1987 Sep;6(9):2597–2606. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Lankes WT, Furthmayr H. Moesin: a member of the protein 4.1-talin-ezrin family of proteins. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8297–8301. [PMC free article] [PubMed]
  • Pakkanen R. Immunofluorescent and immunochemical evidence for the expression of cytovillin in the microvilli of a wide range of cultured human cells. J Cell Biochem. 1988 Sep;38(1):65–75. [PubMed]
  • Pakkanen R, Hedman K, Turunen O, Wahlström T, Vaheri A. Microvillus-specific Mr 75,000 plasma membrane protein of human choriocarcinoma cells. J Histochem Cytochem. 1987 Aug;35(8):809–816. [PubMed]
  • Pakkanen R, von Bonsdorff CH, Turunen O, Wahlström T, Vaheri A. Redistribution of Mr 75,000 plasma membrane protein, cytovillin, into newly formed microvilli in herpes simplex and Semliki Forest virus infected human embryonal fibroblasts. Eur J Cell Biol. 1988 Aug;46(3):435–443. [PubMed]
  • Pasternack GR, Anderson RA, Leto TL, Marchesi VT. Interactions between protein 4.1 and band 3. An alternative binding site for an element of the membrane skeleton. J Biol Chem. 1985 Mar 25;260(6):3676–3683. [PubMed]
  • Rees DJ, Ades SE, Singer SJ, Hynes RO. Sequence and domain structure of talin. Nature. 1990 Oct 18;347(6294):685–689. [PubMed]
  • Sato N, Funayama N, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. A gene family consisting of ezrin, radixin and moesin. Its specific localization at actin filament/plasma membrane association sites. J Cell Sci. 1992 Sep;103(Pt 1):131–143. [PubMed]
  • Turunen O, Winqvist R, Pakkanen R, Grzeschik KH, Wahlström T, Vaheri A. Cytovillin, a microvillar Mr 75,000 protein. cDNA sequence, prokaryotic expression, and chromosomal localization. J Biol Chem. 1989 Oct 5;264(28):16727–16732. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...