ERM proteins and merlin: integrators at the cell cortex (original) (raw)

• Sato, N. et al. A gene family consisting of ezrin, radixin and moesin. Its specific localization at actin filament/plasma membrane association sites. J. Cell Sci. 103, 131–143 (1992).
  CAS PubMed Google Scholar
• 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. 97, 425–432 (1983).This paper reports on the original identification of ezrin as a component of microvillar cytoskeletons, its purification and localization to cell-surface microvilli of cultured cells.
  CAS PubMed Google Scholar
• Pakkanen, R., Hedman, K., Turunen, O., Wahlstrom, T. & Vaheri, A. Microvillus-specific Mr 75,000 plasma membrane protein of human choriocarcinoma cells. J. Histochem. Cytochem. 35, 809–816 (1987).
  CAS PubMed Google Scholar
• Gould, K. L., Cooper, J. A., Bretscher, A. & Hunter, T. The protein-tyrosine kinase substrate, p81, is homologous to a chicken microvillar core protein. J. Cell Biol. 102, 660–669 (1986).
  CAS PubMed Google Scholar
• 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. 105, 1025–1043 (1993).
  CAS PubMed Google Scholar
• 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. 108, 2369–2382 (1989).The first description of radixin.
  CAS PubMed Google Scholar
• Amieva, M. R., Wilgenbus, K. K. & Furthmayr, H. Radixin is a component of hepatocyte microvilli in situ. Exp. Cell Res. 210, 140–144 (1994).
  CAS PubMed Google Scholar
• Lankes, W., Griesmacher, A., Grunwald, J., Schwartz-Albiez, R. & Keller, R. A heparin-binding protein involved in inhibition of smooth-muscle cell proliferation. Biochem. J. 251, 831–842 (1988).
  CAS PubMed PubMed Central Google Scholar
• Gould, K. L., Bretscher, A., Esch, F. S. & Hunter, T. cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. EMBO J. 8, 4133–4142 (1989).
  CAS PubMed PubMed Central Google Scholar
• Lankes, W. T. & Furthmayr, H. Moesin: a member of the protein 4.1–talin–ezrin family of proteins. Proc. Natl Acad. Sci. USA 88, 8297–8301 (1991).This study showed that moesin is closely related to ezrin.
  CAS PubMed PubMed Central Google Scholar
• Funayama, N., Nagafuchi, A., Sato, N., Tsukita, S. & Tsukita, S. Radixin is a novel member of the band 4.1 family. J. Cell Biol. 115, 1039–1048 (1991).
  CAS PubMed Google Scholar
• Trofatter, J. A. et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 75, 826 (1993).
  CAS PubMed Google Scholar
• Rouleau, G. A. et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363, 515–521 (1993).Together with reference 12 , this study showed that the complementary DNA that encodes the product of the Neurofibromatosis 2 tumour-suppressor gene is related to the ERM family.
  CAS PubMed Google Scholar
• Gusella, J. F., Ramesh, V., MacCollin, M. & Jacoby, L. B. Merlin: the neurofibromatosis 2 tumor suppressor. Biochim. Biophys. Acta 1423, M29–M36 (1999).
  CAS PubMed Google Scholar
• Bretscher, A., Chamber, C., Nguyen, R. & Reczek, D. ERM-merlin and EBP50 protein families in plasma membrane organization and function. Annu. Rev. Cell Dev. Biol. 16, 113–143 (2000).
  CAS PubMed Google Scholar
• Mangeat, P., Roy, C. & Martin, M. ERM proteins in cell adhesion and membrane dynamics. Trends Cell Biol. 9, 187–192 (1999).
  CAS PubMed Google Scholar
• Tsukita, S. & Yonemura, S. Cortical actin organization: lessons from ERM (ezrin/radixin/moesin) proteins. J. Biol. Chem. 274, 34507–34510 (1999).
  CAS PubMed Google Scholar
• Doi, Y. et al. Normal development of mice and unimpaired cell adhesion/cell motility/actin-based cytoskeleton without compensatory up-regulation of ezrin or radixin in moesin gene knockout. J. Biol. Chem. 274, 2315–2321 (1999).
  CAS PubMed Google Scholar
• Takeuchi, K. et al. Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members. J. Cell Biol. 125, 1371–1384 (1994).Using antisense oligonucleotides to suppress the expression of ERM proteins, this study showed that ERM proteins are necessary for the presence of microvilli on cultured cells.
  CAS PubMed Google Scholar
• Allenspach, E. J. et al. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 15, 739–750 (2001).
  CAS PubMed Google Scholar
• Kaul, S. C. et al. Identification of a 55-kDa ezrin-related protein that induces cytoskeletal changes and localizes to the nucleolus. Exp. Cell Res. 250, 51–61 (1999).
  CAS PubMed Google Scholar
• Crepaldi, T., Gautreau, A., Comoglio, P. M., Louvard, D. & Arpin, M. Ezrin is an effector of hepatocyte growth factor-mediated migration and morphogenesis in epithelial cells. J. Cell Biol. 138, 423–434 (1997).
  CAS PubMed PubMed Central Google Scholar
• McClatchey, A. I., Saotome, I., Ramesh, V., Gusella, J. F. & Jacks, T. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev. 11, 1253–1265 (1997).This paper reports the first mouse knockout of the Nf2 gene, which shows that merlin is essential for early development.
  CAS PubMed Google Scholar
• Fehon, R. G., Oren, T., LaJeunesse, D. R., Melby, T. E. & McCartney, B. M. Isolation of mutations in the Drosophila homologues of the human Neurofibromatosis 2 and yeast CDC42 genes using a simple and efficient reverse-genetic method. Genetics 146, 245–252 (1997).
  CAS PubMed PubMed Central Google Scholar
• Gusella, J. F., Ramesh, V., MacCollin, M. & Jacoby, L. B. Neurofibromatosis 2: loss of merlin's protective spell. Curr. Opin. Genet. Dev. 6, 87–92 (1996).
  CAS PubMed Google Scholar
• Gary, R. & Bretscher, A. Heterotypic and homotypic associations between ezrin and moesin, two putative membrane-cytoskeletal linking proteins. Proc. Natl Acad. Sci. USA 90, 10846–10850 (1993).
  CAS PubMed PubMed Central Google Scholar
• Gary, R. & Bretscher, A. Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site. Mol. Biol. Cell 6, 1061–1075 (1995).The intramolecular FERM–C-ERMAD interaction is described and mapped, and the idea that ERM proteins are subject to conformational regulation is proposed.
  CAS PubMed PubMed Central Google Scholar
• Berryman, M., Gary, R. & Bretscher, A. Ezrin oligomers are major cytoskeletal components of placental microvilli: a proposal for their involvement in cortical morphogenesis. J. Cell Biol. 131, 1231–1242 (1995).
  CAS PubMed Google Scholar
• Bretscher, A., Gary, R. & Berryman, M. Soluble ezrin purified from placenta exists as stable monomers and elongated dimers with masked C-terminal ezrin–radixin–moesin association domains. Biochemistry 34, 16830–16837 (1995).
  CAS PubMed Google Scholar
• Magendantz, M., Henry, M. D., Lander, A. & Solomon, F. Interdomain interactions of radixin in vitro. J. Biol. Chem. 270, 25324–25327 (1995).
  CAS PubMed Google Scholar
• Martin, M. et al. Ezrin NH2-terminal domain inhibits the cell extension activity of the COOH-terminal domain. J. Cell. Biol. 128, 1081–1093 (1995).
  CAS PubMed Google Scholar
• Henry, M. D., Gonzalez Agosti, C. & Solomon, F. Molecular dissection of radixin: distinct and interdependent functions of the amino- and carboxy-terminal domains. J. Cell Biol. 129, 1007–1022 (1995).
  CAS PubMed Google Scholar
• Reczek, D. & Bretscher, A. The carboxyl-terminal region of EBP50 binds to a site in the amino-terminal domain of ezrin that is masked in the dormant molecule. J. Biol. Chem. 273, 18452–18458 (1998).This paper used biochemical studies to prove that the binding site of EBP50 on the FERM domain is masked by the FERM–C-ERMAD interaction in dormant ezrin, which validates the conformational-regulation hypothesis.
  CAS PubMed Google Scholar
• Takahashi, K. et al. Direct interaction of the Rho GDP dissociation inhibitor with ezrin/radixin/moesin initiates the activation of the Rho small G protein. J. Biol. Chem. 272, 23371–23375 (1997).
  CAS PubMed Google Scholar
• Ishikawa, H. et al. Structural conversion between open and closed forms of radixin: low-angle shadowing electron microscopy. J. Mol. Biol. 310, 973–978 (2001).
  CAS PubMed Google Scholar
• Gautreau, A., Louvard, D. & Arpin, M. Morphogenic effects of ezrin require a phosphorylation-induced transition from oligomers to monomers at the plasma membrane. J. Cell Biol. 150, 193–203 (2000).
  CAS PubMed PubMed Central Google Scholar
• Nakamura, F., Amieva, M. R. & Furthmayr, H. Phosphorylation of threonine 558 in the carboxyl-terminal actin-binding domain of moesin by thrombin activation of human platelets. J. Biol. Chem. 270, 31377–31385 (1995).
  CAS PubMed Google Scholar
• Matsui, T. et al. Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J. Cell Biol. 140, 647–657 (1998).The in vitro demonstration that Rho-kinase can phosphorylate a specific threonine in the carboxy-terminal region of ERM proteins, which reduces the FERM–C-ERMAD interaction, but has no effect on the F-actin-binding site.
  Article CAS PubMed PubMed Central Google Scholar
• Oshiro, N., Fukata, Y. & Kaibuchi, K. Phosphorylation of moesin by Rho-associated kinase (Rho-kinase) plays a crucial role in the formation of microvilli-like structures. J. Biol. Chem. 273, 34663–34666 (1998).
  CAS PubMed Google Scholar
• Hayashi, K., Yonemura, S., Matsui, T., Tsukita, S. & Tsukita, S. Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues. J. Cell Sci. 112, 1149–1158 (1999).
  CAS PubMed Google Scholar
• Tran Quang, C., Gautreau, A., Arpin, M. & Treisman, R. Ezrin function is required for ROCK-mediated fibroblast transformation by the net and dbl oncogenes. EMBO J. 19, 4565–4576 (2000).
  CAS PubMed PubMed Central Google Scholar
• Ng, T. et al. Ezrin is a downstream effector of trafficking PKC–integrin complexes involved in the control of cell motility. EMBO J. 20, 2723–2741 (2001).
  CAS PubMed PubMed Central Google Scholar
• Pietromonaco, S. F., Simons, P. C., Altman, A. & Elias, L. Protein kinase C-θ phosphorylation of moesin in the actin-binding sequence. J. Biol. Chem. 273, 7594–7603 (1998).
  CAS PubMed Google Scholar
• Simons, P. C., Pietromonaco, S. F., Reczek, D., Bretscher, A. & Elias, L. C-terminal threonine phosphorylation activates ERM proteins to link the cell's cortical lipid bilayer to the cytoskeleton. Biochem. Biophys. Res. Commun. 253, 561–565 (1998).
  CAS PubMed Google Scholar
• Yonemura, S., Matsui, T. & Tsukita, S. Rho-dependent and-independent activation mechanisms of ezrin/radixin/moesin proteins: an essential role for polyphosphoinositides in vivo. J. Cell Sci. 115, 2569–2580 (2002).
  CAS PubMed Google Scholar
• Hirao, M. et al. Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J. Cell Biol. 135, 37–51 (1996).This study proposed roles for PtdIns(4,5)P 2 and Rho-signalling pathways in ERM protein regulation.
  CAS PubMed Google Scholar
• Yonemura, S. et al. Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. J. Cell Biol. 140, 885–895 (1998).Together with reference 68 , this report provided the first identification of ERM-binding regions in the cytoplasmic tails of membrane proteins.
  CAS PubMed PubMed Central Google Scholar
• Nakamura, F., Huang, L., Pestonjamasp, K., Luna, E. J. & Furthmayr, H. Regulation of F-actin binding to platelet moesin in vitro by both phosphorylation of threonine 558 and polyphosphatidylinositides. Mol. Biol. Cell 10, 2669–2685 (1999).
  CAS PubMed PubMed Central Google Scholar
• Niggli, V., Andreoli, C., Roy, C. & Mangeat, P. Identification of a phosphatidylinositol-4,5-bisphosphate-binding domain in the N-terminal region of ezrin. FEBS Lett. 376, 172–176 (1995).
  CAS PubMed Google Scholar
• Barret, C., Roy, C., Montcourrier, P., Mangeat, P. & Niggli, V. Mutagenesis of the phosphatidylinositol 4,5-bisphosphate (PIP2) binding site in the NH2-terminal domain of ezrin correlates with its altered cellular distribution. J. Cell Biol. 151, 1067–1080 (2000).
  CAS PubMed PubMed Central Google Scholar
• Pearson, M., Reczek, D., Bretscher, A. & Karplus, P. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101, 259–270 (2000).This study reported the first structure of a FERM domain, as well as the FERM–C-ERMAD complex.
  CAS PubMed Google Scholar
• Hamada, K., Shimizu, T., Matsui, T., Tsukita, S. & Hakoshima, T. Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. EMBO J. 19, 4449–4462 (2000).This study reported the first structure of the free (and presumably active) FERM domain and, by comparison with the structure of Pearson et al . (reference 51 ), described the structural changes that are induced after C-ERMAD release.
  CAS PubMed PubMed Central Google Scholar
• Edwards, S. D. & Keep, N. H. The 2.7 Å crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation. Biochemistry 40, 7061–7068 (2001).
  CAS PubMed Google Scholar
• Zhou, Y. J. et al. Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. Mol. Cell 8, 959–969 (2001).
  CAS PubMed Google Scholar
• Gu, M. & Majerus, P. W. The properties of the protein tyrosine phosphatase PTPMEG. J. Biol. Chem. 271, 27751–27759 (1996).
  CAS PubMed Google Scholar
• Johnson, R. P. & Craig, S. W. F-actin binding site masked by the intramolecular association of vinculin head and tail domains. Nature 373, 261–264 (1995).
  CAS PubMed Google Scholar
• Johnson, R. P. & Craig, S. W. Actin activates a cryptic dimerization potential of the vinculin tail domain. J. Biol. Chem. 275, 95–105 (2000).
  CAS PubMed Google Scholar
• Rohatgi, R. et al. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97, 221–231 (1999).
  CAS PubMed Google Scholar
• Alberts, A. S. Identification of a carboxyl-terminal diaphanous-related formin homology protein autoregulatory domain. J. Biol. Chem. 276, 2824–2830 (2001).
  CAS PubMed Google Scholar
• 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. 108, 921–930 (1989).
  CAS PubMed Google Scholar
• Turunen, O., Wahlstrom, T. & Vaheri, A. Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family. J. Cell Biol. 126, 1445–1453 (1994).This study identified the F-actin-binding site in the tail of ezrin.
  CAS PubMed Google Scholar
• Pestonjamasp, K. et al. Moesin, ezrin, and p205 are actin-binding proteins associated with neutrophil plasma membranes. Mol. Biol. Cell 6, 247–259 (1995).
  CAS PubMed PubMed Central Google Scholar
• Berryman, M. & Bretscher, A. Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli. Mol. Biol. Cell 11, 1509–1521 (2000).
  CAS PubMed PubMed Central Google Scholar
• Roy, C., Martin, M. & Mangeat, P. A dual involvement of the amino-terminal domain of ezrin in F- and G-actin binding. J. Biol. Chem. 272, 20088–20095 (1997).
  CAS PubMed Google Scholar
• Martin, M., Roy, C., Montcourrier, P., Sahuquet, A. & Mangeat, P. Three determinants in ezrin are responsible for cell extension activity. Mol. Biol. Cell 8, 1543–1557 (1997).
  CAS PubMed PubMed Central Google Scholar
• Marchesi, V. T. Stabilizing infrastructure of cell membranes. Annu. Rev. Cell Biol. 1, 531–561 (1985).
  CAS PubMed Google Scholar
• Tsukita, S. et al. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J. Cell. Biol. 126, 391–401 (1994).
  CAS PubMed Google Scholar
• Legg, J. W. & Isacke, C. M. Identification and functional analysis of the ezrin-binding site in the hyaluronan receptor, CD44. Curr. Biol. 8, 705–708 (1998).
  CAS PubMed Google Scholar
• Legg, J. W., Lewis, C. A., Parsons, M., Ng, T. & Isacke, C. M. A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility. Nature Cell Biol. 4, 399–407 (2002).
  CAS PubMed Google Scholar
• Heiska, L. et al. Association of ezrin with intercellular adhesion molecule-1 and-2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4,5-bisphosphate. J. Biol. Chem. 273, 21893–21900 (1998).
  CAS PubMed Google Scholar
• Helander, T. S. et al. ICAM-2 redistributed by ezrin as a target for killer cells. Nature 382, 265–268 (1996).The first evidence for a biological function of ezrin.
  CAS PubMed Google Scholar
• Shaw, A. S. FERMing up the synapse. Immunity 15, 683–686 (2001).
  CAS PubMed Google Scholar
• Delon, J., Kaibuchi, K. & Germain, R. N. Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. Immunity 15, 691–701 (2001).
  CAS PubMed Google Scholar
• Roumier, A. et al. The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation. Immunity 15, 715–728 (2001).
  CAS PubMed Google Scholar
• Denker, S. P., Huang, D. C., Orlowski, J., Furthmayr, H. & Barber, D. L. Direct binding of the Na–H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H+ translocation. Mol. Cell 6, 1425–1436 (2000).
  CAS PubMed Google Scholar
• Yun, C. H., Lamprecht, G., Forster, D. V. & Sidor, A. NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin. J. Biol. Chem. 273, 25856–25863 (1998).
  CAS PubMed Google Scholar
• Reczek, D. & Bretscher, A. Identification of EPI64, a TBC/RabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP. J. Cell Biol. 153, 191–206 (2001).
  CAS PubMed PubMed Central Google Scholar
• Weinman, E. J., Minkoff, C. & Shenolikar, S. Signal complex regulation of renal transport proteins: NHERF and regulation of NHE3 by PKA. Am. J. Physiol. Renal Physiol. 279, F393–F399 (2000).
  CAS PubMed Google Scholar
• Weinman, E. J. New functions for the NHERF family of proteins. J. Clin. Invest. 108, 185–186 (2001).
  CAS PubMed PubMed Central Google Scholar
• Weinman, E. J. & Shenolikar, S. The Na–H exchanger regulatory factor. Exp. Nephrol. 5, 449–452 (1997).
  CAS PubMed Google Scholar
• Weinman, E. J., Steplock, D., Wade, J. B. & Shenolikar, S. Ezrin binding domain-deficient NHERF attenuates cAMP-mediated inhibition of Na+/H+ exchange in OK cells. Am. J. Physiol. Renal Physiol. 281, F374–F380 (2001).
  CAS PubMed Google Scholar
• Dransfield, D. T. et al. Ezrin is a cyclic AMP-dependent protein kinase anchoring protein. EMBO J. 16, 35–43 (1997).
  CAS PubMed PubMed Central Google Scholar
• Wang, S., Raab, R. W., Schatz, P. J., Guggino, W. B. & Li, M. Peptide binding consensus of the NHE-RF–PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane conductance regulator (CFTR). FEBS Lett. 427, 103–108 (1998).
  CAS PubMed Google Scholar
• Short, D. B. et al. An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton. J. Biol. Chem. 273, 19797–19801 (1998).
  CAS PubMed Google Scholar
• Hall, R. A. et al. A C-terminal motif found in the β2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. Proc. Natl Acad. Sci. USA 95, 8496–8501 (1998).
  CAS PubMed PubMed Central Google Scholar
• Hall, R. A. et al. The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 392, 626–630 (1998).
  CAS PubMed Google Scholar
• Cao, T. T., Deacon, H. W., Reczek, D., Bretscher, A. & von Zastrow, M. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the β2-adrenergic receptor. Nature 401, 286–290 (1999).
  CAS PubMed Google Scholar
• Yun, C. H. et al. cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc. Natl Acad. Sci. USA 94, 3010–3015 (1997).
  CAS PubMed PubMed Central Google Scholar
• Maudsley, S. et al. Platelet-derived growth factor receptor association with Na+/H+ exchanger regulatory factor potentiates receptor activity. Mol. Cell. Biol. 20, 8352–8363 (2000).
  CAS PubMed PubMed Central Google Scholar
• Takeda, T., McQuistan, T., Orlando, R. A. & Farquhar, M. G. Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J. Clin. Invest. 108, 289–301 (2001).
  CAS PubMed PubMed Central Google Scholar
• Matsui, T., Yonemura, S., Tsukita, S. & Tsukita, S. Activation of ERM proteins in vivo by rho involves phosphatidylinositol 4-phosphate 5-kinase and not ROCK kinases. Curr. Biol. 9, 1259–1262 (1999).
  CAS PubMed Google Scholar
• Fukata, Y. et al. Association of the myosin-binding subunit of myosin phosphatase and moesin: dual regulation of moesin phosphorylation by Rho-associated kinase and myosin phosphatase. J. Cell Biol. 141, 409–418 (1998).
  CAS PubMed PubMed Central Google Scholar
• Shaw, R. J., Henry, M., Solomon, F. & Jacks, T. RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/actin protrusions in fibroblasts. Mol. Biol. Cell 9, 403–419 (1998).
  CAS PubMed PubMed Central Google Scholar
• Kotani, H., Takaishi, K., Sasaki, T. & Takai, Y. Rho regulates association of both the ERM family and vinculin with the plasma membrane in MDCK cells. Oncogene 14, 1705–1713 (1997).
  CAS PubMed Google Scholar
• Mackay, D. J., Esch, F., Furthmayr, H. & Hall, A. Rho- and Rac-dependent assembly of focal adhesion complexes and actin filaments in permeabilized fibroblasts: an essential role for ezrin/radixin/moesin proteins. J. Cell Biol. 138, 927–938 (1997).
  CAS PubMed PubMed Central Google Scholar
• Lamb, R. F. et al. The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. Nature Cell Biol. 2, 281–287 (2000).
  CAS PubMed Google Scholar
• Shimizu, T. et al. Structural basis for Neurofibromatosis type 2. Crystal structure of the merlin FERM domain. J. Biol. Chem. 277, 10332–10336 (2002).
  CAS PubMed Google Scholar
• Kang, B. S., Cooper, D. R., Devedjiev, Y., Derewenda, U. & Derewenda, Z. S. The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product. Acta Crystallogr. D Biol. Crystallogr. 58, 381–391 (2002).
  PubMed Google Scholar
• McCartney, B. M. & Fehon, R. G. Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin. J. Cell Biol. 133, 843–852 (1996).
  CAS PubMed Google Scholar
• Xu, H. M. & Gutmann, D. H. Merlin differentially associates with the microtubule and actin cytoskeleton. J. Neurosci. Res. 51, 403–415 (1998).
  CAS PubMed Google Scholar
• James, M. F., Manchanda, N., Gonzalez-Agosti, C., Hartwig, J. H. & Ramesh, V. The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association. Biochem. J. 356, 377–386 (2001).
  CAS PubMed PubMed Central Google Scholar
• Brault, E. et al. Normal membrane localization and actin association of the NF2 tumor suppressor protein are dependent on folding of its N-terminal domain. J. Cell Sci. 114, 1901–1912 (2001).
  CAS PubMed Google Scholar
• Scherer, S. S., Xu, T., Crino, P., Arroyo, E. J. & Gutmann, D. H. Ezrin, radixin, and moesin are components of Schwann cell microvilli. J. Neurosci. Res. 65, 150–164 (2001).
  CAS PubMed Google Scholar
• LaJeunesse, D. R., McCartney, B. M. & Fehon, R. G. Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization. J. Cell Biol. 141, 1589–1599 (1998).This study showed that merlin regulates cell proliferation in Drosophila , and the FERM domain provides all the essential functions of Drosophila merlin.
  CAS PubMed PubMed Central Google Scholar
• Stokowski, R. P. & Cox, D. R. Functional analysis of the neurofibromatosis type 2 protein by means of disease-causing point mutations. Am. J. Hum. Genet. 66, 873–891 (2000).
  CAS PubMed PubMed Central Google Scholar
• Meng, J. J. et al. Interaction between two isoforms of the NF2 tumor suppressor protein, merlin, and between merlin and ezrin, suggests modulation of ERM proteins by merlin. J. Neurosci. Res. 62, 491–502 (2000).
  CAS PubMed Google Scholar
• Gronholm, M. et al. Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin. J. Cell Sci. 112, 895–904 (1999).
  CAS PubMed Google Scholar
• Gonzalez-Agosti, C., Wiederhold, T., Herndon, M. E., Gusella, J. & Ramesh, V. Interdomain interaction of merlin isoforms and its influence on intermolecular binding to NHE-RF. J. Biol. Chem. 274, 34438–34442 (1999).
  CAS PubMed Google Scholar
• Sherman, L. et al. Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene 15, 2505–2509 (1997).
  CAS PubMed Google Scholar
• Nguyen, R., Reczek, D. & Bretscher, A. Hierarchy of merlin and ezrin N- and C-terminal domain interactions in homo- and heterotypic associations and their relationship to binding of scaffolding proteins EBP50 and E3KARP. J. Biol. Chem. 276, 7621–7629 (2001).
  CAS PubMed Google Scholar
• Gutmann, D. H. et al. The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the 'open' conformation and suppresses cell growth and motility. Hum. Mol. Genet. 10, 825–834 (2001).
  CAS PubMed Google Scholar
• Maeda, M., Matsui, T., Imamura, M., Tsukita, S. & Tsukita, S. Expression level, subcellular distribution and Rho-GDI binding affinity of merlin in comparison with ezrin/radixin/moesin proteins. Oncogene 18, 4788–4797 (1999).
  CAS PubMed Google Scholar
• Scoles, D. R. et al. Neurofibromatosis 2 tumour suppressor schwannomin interacts with βII-spectrin. Nature Genet. 18, 354–359 (1998).
  CAS PubMed Google Scholar
• Xiao, G. H., Beeser, A., Chernoff, J. & Testa, J. R. p21-activated kinase links Rac/Cdc42 signaling to Merlin. J. Biol. Chem. 21, 21 (2001).
  CAS Google Scholar
• Kissil, J. L., Johnson, K. C., Eckman, M. S. & Jacks, T. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J. Biol. Chem. 277, 10394–10399 (2002).
  CAS PubMed Google Scholar
• Shaw, R. J., McClatchey, A. I. & Jacks, T. Regulation of the neurofibromatosis type 2 tumor suppressor protein, merlin, by adhesion and growth arrest stimuli. J. Biol. Chem. 273, 7757–7764 (1998).
  CAS PubMed Google Scholar
• Shaw, R. J. et al. The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Dev. Cell 1, 63–72 (2001).This study showed that merlin functions downstream of Rac in a signalling pathway.
  CAS PubMed Google Scholar
• Morrison, H. et al. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 15, 968–980 (2001).Merlin is reported to confer its tumour-suppressing function through interaction with the cytoplasmic tail of CD44 in response to elevated levels of hyaluronate, the ligand for CD44.
  CAS PubMed PubMed Central Google Scholar
• LaJeunesse, D. R., McCartney, B. M. & Fehon, R. G. A systematic screen for dominant second-site modifiers of Merlin/NF2 phenotypes reveals an interaction with blistered/DSRF and scribbler. Genetics 158, 667–679 (2001).
  CAS PubMed PubMed Central Google Scholar
• Chishti, A. H. et al. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem. Sci. 23, 281–282 (1998).
  CAS PubMed Google Scholar
• Thompson, J. D., Higgins, D. G. & Gibson, T. J. CLUSTALW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994).
  CAS PubMed PubMed Central Google Scholar
• Girault, J. A., Labesse, G., Mornon, J. P. & Callebaut, I. Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure and signal transduction. Mol. Med. 4, 751–769 (1998).
  CAS PubMed PubMed Central Google Scholar
• Edwards, K., Davis, T., Marcey, D., Kurihara, J. & Yamamoto, D. Comparative analysis of the Band 4.1/ezrin-related protein tyrosine phosphatase Pez from two Drosophila species: implications for structure and function. Gene 275, 195–205 (2001).
  CAS PubMed Google Scholar
• Andersen, J. N. et al. Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol. Cell. Biol. 21, 7117–7136 (2001).
  CAS PubMed PubMed Central Google Scholar
• McClatchey, A. I. et al. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev. 12, 1121–1133 (1998).
  CAS PubMed PubMed Central Google Scholar
• Giovannini, M. et al. Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein. Genes Dev. 13, 978–986 (1999).
  CAS PubMed PubMed Central Google Scholar
• Kalamarides, M. et al. Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse. Genes Dev. 16, 1060–1065 (2002).
  CAS PubMed PubMed Central Google Scholar
• McCartney, B. M., Kulikauskas, R. M., LaJeunesse, D. R. & Fehon, R. G. The neurofibromatosis-2 homologue, merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation. Development 127, 1315–1324 (2000).
  CAS PubMed Google Scholar
• Serrador, J. M. et al. CD43 interacts with moesin and ezrin and regulates its redistribution to the uropods of T lymphocytes at the cell–cell contacts. Blood 91, 4632–4644 (1998).
  CAS PubMed Google Scholar
• Serrador, J. M. et al. Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization. J. Cell Biol. 138, 1409–1423 (1997).
  CAS PubMed PubMed Central Google Scholar
• Ivetic, A., Deka, J., Ridley, A. & Ager, A. The cytoplasmic tail of L-selectin interacts with members of the ezrin–radixin–moesin (ERM) family of proteins: activation dependent binding of moesin but not ezrin. J. Biol. Chem. 8, 8 (2001).
  Google Scholar
• Reczek, D., Berryman, M. & Bretscher, A. Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin–radixin–moesin family. J. Cell Biol. 139, 169–179 (1997).The description of the first PDZ-containing apical scaffolding protein that binds the ERM family.
  CAS PubMed PubMed Central Google Scholar
• Bonilha, V. L. & Rodriguez-Boulan, E. Polarity and developmental regulation of two PDZ proteins in the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 42, 3274–3282 (2001).
  CAS PubMed Google Scholar
• Granes, F., Urena, J. M., Rocamora, N. & Vilaro, S. Ezrin links syndecan-2 to the cytoskeleton. J. Cell Sci. 113, 1267–1276 (2000).
  CAS PubMed Google Scholar
• Takahashi, K. et al. Interaction of radixin with Rho small G protein GDP/GTP exchange protein Dbl. Oncogene 16, 3279–3284 (1998).
  PubMed Google Scholar
• Poullet, P. et al. Ezrin interacts with focal adhesion kinase and induces its activation independently of cell-matrix adhesion. J. Biol. Chem. 276, 37686–37691 (2001).
  CAS PubMed Google Scholar
• Gautreau, A., Poullet, P., Louvard, D. & Arpin, M. Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway. Proc. Natl Acad. Sci. USA 96, 7300–7305 (1999).
  CAS PubMed PubMed Central Google Scholar
• Parlato, S. et al. CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway. EMBO J. 19, 5123–5134 (2000).
  CAS PubMed PubMed Central Google Scholar
• Mykkanen, O. M. et al. Characterization of human palladin, a microfilament-associated protein. Mol. Biol. Cell 12, 3060–3073 (2001).
  CAS PubMed PubMed Central Google Scholar