Regulation of cortical structure by the ezrin-radixin-moesin protein family

Current Opinion in Cell Biology

Volumn 11, Issue 1, 1999, Pages 109-116

  Bretscher, Anthony ^a  

^a Section of Cardiology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; CELL ADHESION MOLECULE; EZRIN; MOESIN; RADIXIN; TRANSMEMBRANE CONDUCTANCE REGULATOR;

AMINO TERMINAL SEQUENCE; ARTICLE; CELL SURFACE; CYTOSKELETON; EPITHELIUM CELL; EXTRACELLULAR MATRIX; LYMPHOCYTE; PRIORITY JOURNAL;

EID: 0033005974     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(99)80013-1     Document Type: Article

References (56)

1. Bretscher A, Reczek D, Berryman M Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci. 110:1997;3011-3018. The most recent review on ERM proteins. It builds the current picture of these proteins from an historical perspective.
2. Tsukita SA, Yonemura S, Tsukita SH ERM (ezrin/radixin/moesin) family: from cytoskeleton to signal transduction. Curr Opin Cell Biol. 9:1997;70-75. A previous review in this series that emphasizes a role for ezrin/radixin/moesin (ERM) proteins in signal transduction.
3. Vaheri A, Carpen O, Heiska L, Helander TS, Jaaskelainen J, Majander-Nordenswan P, Sainio M, Timonen T, Turunen O The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol. 9:1997;659-666. A nicely balanced review that also discusses merlin, the product of the neurofibromatosis 2 tumor suppressor gene product, that is related to ERM proteins and may have overlapping functions with them.
4. Hunter T, Cooper JA Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells. Cell. 24:1981;741-752.
5. Bretscher A Purification of an 80,000-dalton protein that is a component of the isolated microvillus cytoskeleton, and its localization in non-muscle cells. J Cell Biol. 97:1983;425-432.
6. Tsukita SA, Heida Y, Tsukita SH A new 82-kD barbed end-capping protein (radixin) localized in the cell-to-cell junction: purification and characterization. J Cell Biol. 108:1989;2369-2382.
7. Lankes WT, Furthmayr H Moesin: a member of the protein 4.1-talin-ezrin family of proteins. Proc Natl Acad Sci. 88:1991;8297-8301.
8. Takeuchi K, Sato N, Kasahara H, Funayama N, Nagafuchi A, Yonemura S, Tsukita SA, Tsukita SH Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members. J Cell Biol. 125:1994;1371-1384.
9. Crepaldi T, Gautreau A, Comoglio PM, Louvard D, Arpin M Ezrin is an effector of hepatocyte growth-factor-mediated migration and morphogenesis in epithelial cells. J Cell Biol. 138:1997;423-434. This is the first paper to demonstrate that the amino-terminal domain of ezrin can act as a dominant negative. It also provides very strong evidence that phosphorylation of two tyrosines in ezrin (Tyr145 and Tyr353) plays a role in signal transduction.
10. Lamb RF, Ozanne BW, Roy C, McGarry L, Stipp C, Mangeat P, Jay DG Essential functions of ezrin in maintenance of cell shape and lamellipodial extension in normal and transformed fibroblasts. Curr Biol. 7:1997;682-688. MicroCALI (chromophore-assisted laser irradiation) was used to inactivate ezrin in Rat-1 cells. In this technique, antibodies to ezrin are coupled to malachite green and then injected into cells. Laser activation of the malachite green induces the formation of hydroxyl radicals that specifically inactivate the protein bound to the antibody. This approach reveals that loss of ezrin function induces the immediate and reversible loss of membrane ruffles. This is another important study indicating a role for ezrin in maintaining cell surface structures.
11. 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. 6:1995;1061-1075.
12. 2-terminal domain inhibits the cell extension activity of the COOH-terminal domain. J Cell Biol. 128:1995;1081-1093.
13. Henry MD, Agosti CG, Solomon F Molecular dissection of radixin: distinct and interdependent functions of the amino- and carboxy-terminal domains. J Cell Biol. 129:1995;1007-1022.
14. 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. 131:1995;1231-1242.
15. Tsukita SA, Oishi K, Sato N, Sagara J, Kawai A, Tsukita SH ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J Cell Biol. 126:1994;391-401.
16. Hirao M, Sato N, Kondo T, Yonemura S, Monden M, Sasaki T, Takai Y, Tsukita SH, Tsukita SA Regulation mechanism of ERM protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J Cell Biol. 135:1996;37-51.
17. Helander TS, Carpen O, Turunen O, Kovanen PE, Vaheri A, Timonen T ICAM-2 redistributed by ezrin as a target for killer cells. Nature. 382:1996;265-268.
18. •].
19. •].
20. 300 (in the single letter code for amino acids) in the juxtamembrane region were found to be essential for this interaction. Site-directed mutations to render CD44 defective in ezrin binding still allowed CD44 to colocalize with ezrin in microvilli. Therefore the interaction between ezrin and CD44 is not sufficient to localize the receptor to microvilli.
21. •] regions in cytoplasmic tails necessary for interacting with ERM proteins were mapped. In all cases, the positively charged juxtamembrane region is implicated. Moreover, E-caderin fused to the wild-type CD44 tail colocalized with ERM proteins in surface microvilli, whereas constructs with the postively-charged region removed did not. Although it is possible that removal of the positively-charged region might grossly alter the topology of the protein with respect to the membrane, the localization results correlate well with the recovery of moesin in immunoprecipitates of the various constructs. Could all juxtamembrane positively charged amino acid clusters bind ERM proteins? The authors provide examples where this is not the case, so the basis for selectivity remains undetermined.
22. 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. 139:1997;169-179. Using immobilized amino-terminal domains of ezrin and moesin, a new ERM binding protein called EBP50 (ERM binding phosphoprotein of 50 kDa) was identified and the gene encoding it was cloned. EBP50 colocalizes with ezrin in polarized epithelial cells and in cultured cell microvilli and can be co-immunoprecipitated with ezrin from isolated microvilli. It is the first PDZ domain containing protein described that resides in the apical aspect of polarized epithelial cells.
23. 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. 273:1998;18452-18458. The region in the amino-terminal domain of ezrin sufficient for interaction with EBP50 is mapped, and the ezrin binding site of EBP50 localized to the 30 carboxy-terminal residues. The binding site of EBP50 in ezrin is masked in the dormant protein. Analysis of a site directed mutant shows this masking is due to an intramolecular interaction between the N- and C-ERMADs in the wild-type molecule. E3KARP is also reported to bind ezrin and moesin amino-terminal domains.
24. + exchanger. J Clin Investig. 95:1995;2143-2149.
25. + exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci USA. 96:1997;3010-3015.
26. •,28-30]. This group of papers suggests that EBP50 and E3KARP may bind simultaneously to two membrane proteins, although this has yet to be demonstrated directly.
27. Short DB, Trotter KW, Reczek D, Kreda SM, Bretscher A, Boucher RC, Stutts MJ, Milgram SL An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton. J Biol Chem. 273:1998;19797-19801. EBP50 was shown to colocalize with the CFTR (cystic fibrosis transmembrane conductance regulator) and to bind to the carboxy-terminal four residues of the CFTR. Binding can occur through either PDZ domain of EBP50, but the affinity is higher for the first one.
28. Wang S, Raab RW, Schatz PJ, Guggino WB, Li M Peptide binding consensus of the NHE-RF-PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane conductance regulator. FEBS Lett. 427:1998;103-108.
29. + exchange. Nature. 392:1998;626-630.
30. + exchanger regulatory factor family of PDZ proteins. Proc Natl Acad Sci. 95:1998;8496-8501.
31. Dransfield DT, Bradford AJ, Smith J, Martin M, Roy C, Mangeat PH, Goldenring JR Ezrin is a cyclic AMP-dependent protein kinase anchoring protein. EMBO J. 6:1997;35-43. Microsequence data shows that ezrin is the previously identified AKAP78 (A-kinase anchoring protein 78). The regulatory subunit (RII) of protein kinase A binds to all ERM members and the binding site in ezrin was mapped to the region 373-439, perhaps binding to an amphipathic helix in this region. The RII subunit colocalizes with ezrin in stimulated parietal cells. These results provide the first suggestion that ERM proteins might localize regulatory kinases to the cortical cytoskeleton.
32. 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. 126:1994;1445-1453.
33. Pestonjamasp K, Amieva MR, Strassel CP, Nauseef WM, Furthmayr H, Luna EJ Moesin, ezrin, and p205 are actin-binding proteins associated with neutrophil plasma membranes. Mol Biol Cell. 6:1995;247-259.
34. Yao X, Cheng L, Forte JG Biochemical characterization of ezrin-actin interaction. J Biol Chem. 271:1996;7224-7229.
35. 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. 272:1997;20088-20095. Using a solid phase assay with recombinant fragments of ezrin, regions capable of binding F- or G-actin were mapped. Binding of F-actin to the carboxy-terminal region was found to be dependent on the presence of residues near the amino-terminus, a finding different from [32,33]. An actin binding site in the middle of the molecule (residues 279-332) was also uncovered.
36. Martin M, Roy C, Montcourrier P, Sahuquet A, Mangeat P Three determinants in ezrin are responsible for cell extension activity. Mol Biol Cell. 8:1997;1543-1557. Earlier transfection experiments [12] had shown that overexpression of the carboxy-terminal region of ezrin (residues 309-585) in insect Sf9 cells induces long cell extensions. Many other constructs are now shown to induce a similar phenotype. On the basis of these studies, loss of any of three regions are found to induce extensions.
37. Johnson RP, Craig SW F actin binding site masked by the intramolecular association of vinculin head and tail domains. Nature. 373:1995;261-264.
38. Johnson RP, Craig SW An intramolecular association between the head and tail domains of vinculin modulates talin binding. J Biol Chem. 269:1994;12611-12619.
39. Bhartur SG, Goldenring JR Mapping of ezrin dimerization using yeast two-hybrid screen. Biochem Biophys Res Commun. 243:1998;874-877.
40. 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. 376:1995;172-176.
41. Nakamura F, Amieva MR, Furthmayr H Phosphorylation of threonine 558 in the carboxy-terminal actin-binding domain of moesin by thrombin activation of human platelets. J Biol Chem. 270:1996;31377-31385.
42. Shaw RJ, Henry M, Solomon F, Jacks T RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/actin protrusions in fibroblasts. Mol Biol Cell. 9:1998;403-419. Treatment of Swiss 3T3 cells containing epitope tagged radixin with lysophosphatidic acid induces the formation of radixin-containing cell surface structures; this effect in inhibited by C3 transferase, a specific inhibitor of Rho. The same effects can be induced by dominant Rho constructs. During this process, there is a correlation between enhanced phosphorylation of radixin and increased association with the cytoskeleton.
43. Chen J, Mandel LJ Unopposed phosphatase action initiates ezrin dysfunction: a potential mechanism for anoxic injury. Am J Physiol. 273:1997;C710-C716.
44. Kondo T, Takeuchi K, Doi Y, Yonemura S, Nagata S, Tsukita SH, Tsukita SA ERM (ezrin/radixin/moesin)-based molecular mechanism of microvillar breakdown at an early stage of apoptosis. J Cell Biol. 139:1997;749-758.
45. Pietromonaco SF, Simons PC, Altman A, Elias L Protein kinase C-Θ phosphorylation of moesin in the actin-binding sequence. J Biol Chem. 273:1998;7594-7603. A substrate for a lipid stimulated kinase was identified as moesin and the site of phosphophorylation was determined to be Thr558. The moesin kinase is identified as PKC-Θ.
46. Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, Tsukita SA, Tsukita SH Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol. 140:1998;647-657. Rho-kinase phosphorylates Thr564 in a carboxy-terminal fragment of radixin in vitro; full length radixin is a relatively poor substrate. LPA treatment of 3T3 cells enhances phosphorylation of this residue within 30 seconds. Phosphorylation of the carboxy-terminal fragment of radixin has no effect on its ability to cosediment with F-actin, but destroys its ability to interact with radixin N-ERMAD. The authors suggest that in vivo, some other mechanism activates dormant radixin and then Thr564 is phosphorylated to maintain the protein in an active conformation.
47. Krieg J, Hunter T Identification of the two major epidermal growth factor-induced tyrosine phosphorylation sites in the microvillar core protein ezrin. J Biol Chem. 267:1992;19258-19265.
48. Fukata Y, Kimura K, Oshiro N, Saya H, Matsuura Y, Kaibuchi K 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. 141:1998;409-418.
49. Yao X, Thibodeau A, Forte JG Ezrin-calpain I interactions in gastric parietal cells. Am J Physiol. 265:1996;C36.
50. •], RhoGDI competes with the C-ERMAD for binding to the N-ERMAD. Introduction of the amino-terminal domain of radixin into cells should sequester all the RhoGDI with release of Rho and thereby induce Rho-dependent processes: introduction of this domain of radixin indeed induces the formation of stress fibers in serum starved Swiss 3T3 cells.
51. Mackay DJ, 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. 138:1997;927-938.
52. Takahashi K, Sasaki T, Mammoto A, Hotta I, Takaishi K, Imamura H, Nakano K, Kodama A, Takai Y Interaction of radixin with rho small G protein GDP/GTP exchange protein Ddl. Oncogene. 16:1998;3279-3284.
53. Pearson M, Reczek D, Bretscher A, Karplus PA: Crystallographic studies of moesin: a protein that links the actin cytoskeleton to the plasma membrane. Mol Biol Cell 1998, 9: in press (abstract).
54. 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. 105:1993;1025-1043.
55. Simon PC, Pietromonaco SF, Reczek R, Bretscher A, Elias L: C-terminal threonine phosphorylation activates ERM proteins to link the cell's cortical lipid bilayer to the actin cytoskeleton. Biochem Biophys Res Comm 1999: in press.
56. Scherbina A, Bretscher A, Kenney DM, Remold-O'Donnell E: Moesin, a major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain. FEBS Lett 1999, in press.