PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Cell Biol. 1996 May 2; 133(4): 843–852.
PMCID: PMC2120840

Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin

Abstract

Interest in members of the protein 4.1 super-family, which includes the ezrin-radixin-moesin (ERM) group, has been stimulated recently by the discovery that the human neurofibromatosis 2 (NF2) tumor suppressor gene encodes an ERM-like protein, merlin. Although many proteins in this family are thought to act by linking the actin-based cytoskeleton to transmembrane proteins, the cellular functions of merlin have not been defined. To investigate the cellular and developmental functions of these proteins, we have identified and characterized Drosophila homologues of moesin (Dmoesin) and of the NF2 tumor suppressor merlin (Dmerlin). Using specific antibodies, we show that although these proteins are frequently coexpressed in developing tissues, they display distinct subcellular localizations. While Dmoesin is observed in continuous association with the plasma membrane, as is typical for an ERM family protein, Dmerlin is found in punctuate structures at the membrane and in the cytoplasm. Investigation of Dmerlin cultured cells demonstrates that it is associated with endocytic compartments. As a result of these studies, we propose that the merlin protein has unique functions in the cell which differ from those of other ERM family members.

Full Text

The Full Text of this article is available as a PDF (3.9M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Algrain M, Turunen O, Vaheri A, Louvard D, Arpin M. Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker. J Cell Biol. 1993 Jan;120(1):129–139. [PMC free article] [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Banerjee U, Renfranz PJ, Hinton DR, Rabin BA, Benzer S. The sevenless+ protein is expressed apically in cell membranes of developing Drosophila retina; it is not restricted to cell R7. Cell. 1987 Oct 9;51(1):151–158. [PubMed]
  • Banville D, Ahmad S, Stocco R, Shen SH. A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases. J Biol Chem. 1994 Sep 2;269(35):22320–22327. [PubMed]
  • Bennett V. Spectrin-based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm. Physiol Rev. 1990 Oct;70(4):1029–1065. [PubMed]
  • Berryman M, Franck Z, Bretscher A. Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J Cell Sci. 1993 Aug;105(Pt 4):1025–1043. [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]
  • Brown NH, Kafatos FC. Functional cDNA libraries from Drosophila embryos. J Mol Biol. 1988 Sep 20;203(2):425–437. [PubMed]
  • Bunch TA, Grinblat Y, Goldstein LS. Characterization and use of the Drosophila metallothionein promoter in cultured Drosophila melanogaster cells. Nucleic Acids Res. 1988 Feb 11;16(3):1043–1061. [PMC free article] [PubMed]
  • DiMario PJ, Mahowald AP. The effects of pH and weak bases on the in vitro endocytosis of vitellogenin by oocytes of Drosophila melanogaster. Cell Tissue Res. 1986;246(1):103–108. [PubMed]
  • DiMario PJ, Mahowald AP. Female sterile (1) yolkless: a recessive female sterile mutation in Drosophila melanogaster with depressed numbers of coated pits and coated vesicles within the developing oocytes. J Cell Biol. 1987 Jul;105(1):199–206. [PMC free article] [PubMed]
  • Edwards KA, Montague RA, Shepard S, Edgar BA, Erikson RL, Kiehart DP. Identification of Drosophila cytoskeletal proteins by induction of abnormal cell shape in fission yeast. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4589–4593. [PubMed]
  • Fehon RG, Kooh PJ, Rebay I, Regan CL, Xu T, Muskavitch MA, Artavanis-Tsakonas S. Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila. Cell. 1990 May 4;61(3):523–534. [PubMed]
  • Fehon RG, Johansen K, Rebay I, Artavanis-Tsakonas S. Complex cellular and subcellular regulation of notch expression during embryonic and imaginal development of Drosophila: implications for notch function. J Cell Biol. 1991 May;113(3):657–669. [PMC free article] [PubMed]
  • Fehon RG, Dawson IA, Artavanis-Tsakonas S. A Drosophila homologue of membrane-skeleton protein 4.1 is associated with septate junctions and is encoded by the coracle gene. Development. 1994 Mar;120(3):545–557. [PubMed]
  • Franck Z, Gary R, Bretscher A. Moesin, like ezrin, colocalizes with actin in the cortical cytoskeleton in cultured cells, but its expression is more variable. J Cell Sci. 1993 May;105(Pt 1):219–231. [PubMed]
  • Frorath B, Scanarini M, Netter HJ, Abney CC, Liedvogel B, Lakomek HJ, Northemann W. Cloning and expression of antigenic epitopes of the human 68-kDa (U1) ribonucleoprotein antigen in Escherichia coli. Biotechniques. 1991 Sep;11(3):364–371. [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, 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. [PubMed]
  • Greenwald I, Rubin GM. Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells. Cell. 1992 Jan 24;68(2):271–281. [PubMed]
  • Gu MX, York JD, Warshawsky I, Majerus PW. Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5867–5871. [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. [PubMed]
  • MacCollin M, Mohney T, Trofatter J, Wertelecki W, Ramesh V, Gusella J. DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the merlin tumor suppressor in an extended pedigree. JAMA. 1993 Nov 17;270(19):2316–2320. [PubMed]
  • Martuza RL, Eldridge R. Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Engl J Med. 1988 Mar 17;318(11):684–688. [PubMed]
  • Mays RW, Beck KA, Nelson WJ. Organization and function of the cytoskeleton in polarized epithelial cells: a component of the protein sorting machinery. Curr Opin Cell Biol. 1994 Feb;6(1):16–24. [PubMed]
  • Miller KG, Field CM, Alberts BM. Actin-binding proteins from Drosophila embryos: a complex network of interacting proteins detected by F-actin affinity chromatography. J Cell Biol. 1989 Dec;109(6 Pt 1):2963–2975. [PMC free article] [PubMed]
  • Peifer M. The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction. J Cell Sci. 1993 Aug;105(Pt 4):993–1000. [PubMed]
  • Poodry CA. shibire, a neurogenic mutant of Drosophila. Dev Biol. 1990 Apr;138(2):464–472. [PubMed]
  • Rees DJ, Ades SE, Singer SJ, Hynes RO. Sequence and domain structure of talin. Nature. 1990 Oct 18;347(6294):685–689. [PubMed]
  • Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature. 1993 Jun 10;363(6429):515–521. [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]
  • Smith DB, Johnson KS. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. [PubMed]
  • Swanson J. Fluorescent labeling of endocytic compartments. Methods Cell Biol. 1989;29:137–151. [PubMed]
  • Takeuchi K, Sato N, Kasahara H, Funayama N, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members. J Cell Biol. 1994 Jun;125(6):1371–1384. [PMC free article] [PubMed]
  • Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Mar 12;72(5):791–800. [PubMed]
  • Tsukita S, Hieda Y, Tsukita S. A new 82-kD barbed end-capping protein (radixin) localized in the cell-to-cell adherens junction: purification and characterization. J Cell Biol. 1989 Jun;108(6):2369–2382. [PMC free article] [PubMed]
  • Turunen O, Wahlström T, Vaheri A. Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family. J Cell Biol. 1994 Sep;126(6):1445–1453. [PMC free article] [PubMed]
  • van der Bliek AM, Meyerowitz EM. Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature. 1991 May 30;351(6325):411–414. [PubMed]
  • Wells A, Welsh JB, Lazar CS, Wiley HS, Gill GN, Rosenfeld MG. Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. Science. 1990 Feb 23;247(4945):962–964. [PubMed]
  • Yang Q, Tonks NK. Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and talin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5949–5953. [PubMed]
  • Zak NB, Shilo BZ. Localization of DER and the pattern of cell divisions in wild-type and Ellipse eye imaginal discs. Dev Biol. 1992 Feb;149(2):448–456. [PubMed]

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