Advertisement

Ezrin Orchestrates Signal Transduction in Airway Cells

  • Lei-Miao Yin
  • Ting-Ting Duan
  • Luis Ulloa
  • Yong-Qing Yang
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 174)

Abstract

Ezrin is a critical structural protein that organizes receptor complexes and orchestrates their signal transduction. In this study, we review the ezrin-meditated regulation of critical receptor complexes, including the epidermal growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin-meditated regulation of critical pathways associated with asthma, such as the RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA) pathways. Mounting evidence suggests that ezrin plays a role in controlling airway cell function and potentially contributes to respiratory diseases. Ezrin can participate in asthma pathogenesis by affecting bronchial epithelium repair, T lymphocyte regulation, and the contraction of the airway smooth muscle cells. These studies provide new insights for the design of novel therapeutic strategies for asthma treatment.

Keywords

Actin-binding proteins Airway cells Asthma Ezrin 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81473760, 81574058); the Shanghai Talent Development Fund (No. 201610); the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (JZ2016010).

References

  1. Abbattiscianni AC, Favia M, Mancini MT, Cardone RA, Guerra L, Monterisi S, Castellani S, Laselva O, Di Sole F, Conese M, Zaccolo M, Casavola V (2016) Correctors of mutant CFTR enhance subcortical cAMP-PKA signaling through modulating ezrin phosphorylation and cytoskeleton organization. J Cell Sci 129:1128–1140PubMedCrossRefGoogle Scholar
  2. Allenspach EJ, Cullinan P, Tong J, Tang Q, Tesciuba AG, Cannon JL, Takahashi SM, Morgan R, Burkhardt JK, Sperling AI (2001) ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 15:739–750PubMedCrossRefGoogle Scholar
  3. Ammar B, Alice G (2016) ET-1 enhances EGFR phosphorylation via Src activation in asthmatic airway smooth muscle. In: A33. Airway smooth muscle. American Thoracic Society international conference abstracts, American Thoracic Society, p A1347Google Scholar
  4. Anastasiadis PZ, Moon SY, Thoreson MA, Mariner DJ, Crawford HC, Zheng Y, Reynolds AB (2000) Inhibition of RhoA by p120 catenin. Nat Cell Biol 2:637–644PubMedCrossRefGoogle Scholar
  5. Antelmi E, Cardone RA, Greco MR, Rubino R, Di Sole F, Martino NA, Casavola V, Carcangiu M, Moro L, Reshkin SJ (2013) ss1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion. PLoS One 8:e75113PubMedPubMedCentralCrossRefGoogle Scholar
  6. Antoine-Bertrand J, Ghogha A, Luangrath V, Bedford FK, Lamarche-Vane N (2011) The activation of ezrin-radixin-moesin proteins is regulated by netrin-1 through Src kinase and RhoA/Rho kinase activities and mediates netrin-1-induced axon outgrowth. Mol Biol Cell 22:3734–3746PubMedPubMedCentralCrossRefGoogle Scholar
  7. Arij F, Britt RD Jr, Elizabeth RV, Michael AT, Christina MP, Richard JM, Prakash YS (2015) Fluticasone propionate attenuates poly (I:C)-induced ICAM-1 and VCAM-1 in the developing human airway smooth muscle. In: C67. Functional mapping of smooth muscle contractome and relaxome. American Thoracic Society international conference abstracts, American Thoracic Society, p A5000Google Scholar
  8. Baeyens N, Meester CD, Yerna X, Morel N (2011) EBP50 is involved in the regulation of vascular smooth muscle cell migration and cytokinesis. J Cell Biochem 112:2574–2584PubMedCrossRefGoogle Scholar
  9. Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, Sanchez-Madrid F (2002) Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 157:1233–1245PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bretscher A (1983) 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 97:425–432PubMedCrossRefGoogle Scholar
  11. Bretscher A (1989) Rapid phosphorylation and reorganization of ezrin and spectrin accompany morphological changes induced in A-431 cells by epidermal growth factor. J Cell Biol 108:921–930PubMedCrossRefGoogle Scholar
  12. Bretscher A, Reczek D, Berryman M (1997) Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci 110:3011–3018PubMedGoogle Scholar
  13. Brown MJ, Nijhara R, Hallam JA, Gignac M, Yamada KM, Erlandsen SL, Delon J, Kruhlak M, Shaw S (2003) Chemokine stimulation of human peripheral blood T lymphocytes induces rapid dephosphorylation of ERM proteins, which facilitates loss of microvilli and polarization. Blood 102:3890–3899PubMedCrossRefGoogle Scholar
  14. Burgel PR, Nadel JA (2008) Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Eur Respir J 32:1068–1081PubMedCrossRefGoogle Scholar
  15. Burkhardt JK, Carrizosa E, Shaffer MH (2008) The actin cytoskeleton in T cell activation. Annu Rev Immunol 26:233–259PubMedCrossRefGoogle Scholar
  16. Cannon JL, Mody PD, Blaine KM, Chen EJ, Nelson AD, Sayles LJ, Moore TV, Clay BS, Dulin NO, Shilling RA, Burkhardt JK, Sperling AI (2011) CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation. Mol Biol Cell 22:954–963PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cant SH, Pitcher JA (2005) G protein-coupled receptor kinase 2-mediated phosphorylation of ezrin is required for G protein-coupled receptor-dependent reorganization of the actin cytoskeleton. Mol Biol Cell 16:3088–3099PubMedPubMedCentralCrossRefGoogle Scholar
  18. Casalino-Matsuda SM, Monzon ME, Day AJ, Forteza RM (2009) Hyaluronan fragments/CD44 mediate oxidative stress-induced MUC5B up-regulation in airway epithelium. Am J Respir Cell Mol Biol 40:277–285PubMedCrossRefGoogle Scholar
  19. Castellani S, Guerra L, Favia M, Di Gioia S, Casavola V, Conese M (2012) NHERF1 and CFTR restore tight junction organisation and function in cystic fibrosis airway epithelial cells: role of ezrin and the RhoA/ROCK pathway. Lab Investig 92:1527–1540PubMedCrossRefGoogle Scholar
  20. Celik H, Sajwan KP, Selvanathan SP, Marsh BJ, Pai AV, Kont YS, Han J, Minas TZ, Rahim S, Erkizan HV, Toretsky JA, Uren A (2015) Ezrin binds to DEAD-box RNA helicase DDX3 and regulates its function and protein level. Mol Cell Biol 35:3145–3162PubMedPubMedCentralGoogle Scholar
  21. Chambers DN, Bretscher A (2005) Ezrin mutants affecting dimerization and activation. Biochemistry 44:3926–3932PubMedCrossRefGoogle Scholar
  22. Chiappetta C, Leopizzi M, Censi F, Puggioni C, Petrozza V, Rocca CD, Di Cristofano C (2014) Correlation of the Rac1/RhoA pathway with ezrin expression in osteosarcoma. Appl Immunohistochem Mol Morphol 22:162–170PubMedCrossRefGoogle Scholar
  23. Clucas J, Valderrama F (2014) ERM proteins in cancer progression. J Cell Sci 127:267–275PubMedCrossRefGoogle Scholar
  24. Cornez I, Taskén K (2010) Spatiotemporal control of cyclic AMP immunomodulation through the PKA-Csk inhibitory pathway is achieved by anchoring to an ezrin-EBP50-PAG scaffold in effector T cells. FEBS Lett 584:2681–2688PubMedCrossRefGoogle Scholar
  25. Cui Y, Li T, Zhang D, Han J (2010) Expression of ezrin and phosphorylated ezrin (pezrin) in pancreatic ductal adenocarcinoma. Cancer Investig 28:242–247CrossRefGoogle Scholar
  26. D’Amato G, Vitale C, Molino A, Stanziola A, Sanduzzi A, Vatrella A, Mormile M, Lanza M, Calabrese G, Antonicelli L, D’Amato M (2016) Asthma-related deaths. Multidiscip Respir Med 11:37PubMedPubMedCentralCrossRefGoogle Scholar
  27. da Silva AR, Madge L, Soroosh P, Tocker J, Croft M (2015) The TNF family molecules LIGHT and lymphotoxin alphabeta induce a distinct steroid-resistant inflammatory phenotype in human lung epithelial cells. J Immunol 195:2429–2441CrossRefGoogle Scholar
  28. Deming PB, Campbell SL, Stone JB, Rivard RL, Mercier AL, Howe AK (2015) Anchoring of protein kinase A by ERM (ezrin-radixin-moesin) proteins is required for proper netrin signaling through DCC (deleted in colorectal cancer). J Biol Chem 290:5783–5796PubMedPubMedCentralCrossRefGoogle Scholar
  29. Di Sole F, Babich V, Moe OW (2009) The calcineurin homologous protein-1 increases Na(+)/H(+)-exchanger 3 trafficking via ezrin phosphorylation. J Am Soc Nephrol 20:1776–1786PubMedPubMedCentralCrossRefGoogle Scholar
  30. Dransfield DT, Bradford AJ, Smith J, Martin M, Roy C, Mangeat PH, Goldenring JR (1997) Ezrin is a cyclic AMP-dependent protein kinase anchoring protein. EMBO J 16:35–43PubMedPubMedCentralCrossRefGoogle Scholar
  31. Fazioli F, Wong WT, Ullrich SJ, Sakaguchi K, Appella E, Di Fiore PP (1993) The ezrin-like family of tyrosine kinase substrates: receptor-specific pattern of tyrosine phosphorylation and relationship to malignant transformation. Oncogene 8:1335–1345PubMedGoogle Scholar
  32. Fehon RG, McClatchey AI, Bretscher A (2010) Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol 11:276–287PubMedPubMedCentralCrossRefGoogle Scholar
  33. Fievet BT, Gautreau A, Roy C, Del Maestro L, Mangeat P, Louvard D, Arpin M (2004) Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin. J Cell Biol 164:653–659PubMedPubMedCentralCrossRefGoogle Scholar
  34. Fievet B, Louvard D, Arpin M (2007) ERM proteins in epithelial cell organization and functions. Biochim Biophys Acta 1773:653–660PubMedCrossRefGoogle Scholar
  35. Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463:485–492PubMedPubMedCentralCrossRefGoogle Scholar
  36. Fouassier L, Fiorotto R (2015) Ezrin finds its groove in cholangiocytes. Hepatology 61:1467–1470PubMedPubMedCentralCrossRefGoogle Scholar
  37. Fouassier L, Rosenberg P, Mergey M, Saubamea B, Claperon A, Kinnman N, Chignard N, Jacobsson-Ekman G, Strandvik B, Rey C, Barbu V, Hultcrantz R, Housset C (2009) Ezrin-radixin-moesin-binding phosphoprotein (EBP50), an estrogen-inducible scaffold protein, contributes to biliary epithelial cell proliferation. Am J Pathol 174:869–880PubMedPubMedCentralCrossRefGoogle Scholar
  38. Fukasawa H, Obayashi H, Schmieder S, Lee J, Ghosh P, Farquhar MG (2011) Phosphorylation of podocalyxin (Ser415) prevents RhoA and ezrin activation and disrupts its interaction with the actin cytoskeleton. Am J Pathol 179:2254–2265PubMedPubMedCentralCrossRefGoogle Scholar
  39. Fukata Y, Amano M, Kaibuchi K (2001) Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci 22:32–39PubMedCrossRefGoogle Scholar
  40. Gautreau A, Louvard D, Arpin M (2000) Morphogenic effects of ezrin require a phosphorylation-induced transition from oligomers to monomers at the plasma membrane. J Cell Biol 150:193–203PubMedPubMedCentralCrossRefGoogle Scholar
  41. Glare EM, Divjak M, Bailey MJ, Walters EH (2002) Beta-actin and GAPDH housekeeping gene expression in asthmatic airways is variable and not suitable for normalising mRNA levels. Thorax 57:765–770PubMedPubMedCentralCrossRefGoogle Scholar
  42. Gould KL, Cooper JA, Bretscher A, Hunter T (1986) The protein-tyrosine kinase substrate, p81, is homologous to a chicken microvillar core protein. J Cell Biol 102:660–669PubMedCrossRefGoogle Scholar
  43. Gould KL, Bretscher A, Esch FS, Hunter T (1989) cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. EMBO J 8:4133–4142PubMedPubMedCentralCrossRefGoogle Scholar
  44. Hamada K, Shimizu T, Yonemura S, Tsukita S, Tsukita S, Hakoshima T (2003) Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex. EMBO J 22:502–514PubMedPubMedCentralCrossRefGoogle Scholar
  45. Heiska L, Carpen O (2005) Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member. J Biol Chem 280:10244–10252PubMedCrossRefGoogle Scholar
  46. Heiska L, Alfthan K, Gronholm M, Vilja P, Vaheri A, Carpen O (1998) Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate. J Biol Chem 273:21893–21900PubMedCrossRefGoogle Scholar
  47. Hirao M, Sato N, Kondo T, Yonemura S, Monden M, Sasaki T, Takai Y, Tsukita S, Tsukita S (1996) Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J Cell Biol 135:37–51PubMedCrossRefGoogle Scholar
  48. Holgate ST (2000) Epithelial damage and response. Clin Exp Allergy 30(Suppl 1):37–41PubMedCrossRefGoogle Scholar
  49. Homma T, Kato A, Sakashita M, Norton JE, Suh LA, Carter RG, Schleimer RP (2015) Involvement of Toll-like receptor 2 and epidermal growth factor receptor signaling in epithelial expression of airway remodeling factors. Am J Respir Cell Mol Biol 52:471–481PubMedPubMedCentralCrossRefGoogle Scholar
  50. Horvat SJ, Deshpande DA, Yan H, Panettieri RA, Codina J, DuBose TD Jr, Xin W, Rich TC, Penn RB (2012) A-kinase anchoring proteins regulate compartmentalized cAMP signaling in airway smooth muscle. FASEB J 26:3670–3679PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hunter T, Cooper JA (1981) Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells. Cell 24:741–752PubMedCrossRefGoogle Scholar
  52. Iontcheva I, Amar S, Zawawi KH, Kantarci A, Van Dyke TE (2004) Role for moesin in lipopolysaccharide-stimulated signal transduction. Infect Immun 72:2312–2320PubMedPubMedCentralCrossRefGoogle Scholar
  53. Isacke CM, Yarwood H (2002) The hyaluronan receptor, CD44. Int J Biochem Cell Biol 34:718–721PubMedCrossRefGoogle Scholar
  54. Jayasundar JJ, Ju JH, He L, Liu D, Meilleur F, Zhao J, Callaway DJ, Bu Z (2012) Open conformation of ezrin bound to phosphatidylinositol 4,5-bisphosphate and to F-actin revealed by neutron scattering. J Biol Chem 287:37119–37133PubMedPubMedCentralCrossRefGoogle Scholar
  55. Jiang QY, Xia JM, Ding HG, Fei XW, Lin J, Wu RJ (2012) RNAi-mediated blocking of ezrin reduces migration of ectopic endometrial cells in endometriosis. Mol Hum Reprod 18:435–441PubMedCrossRefGoogle Scholar
  56. Jing Y, Renat S, Wu-Lin Z, Ion WC, Michelle RS, Jacqueline S, Robert JK, Yael S-B, Ronald GC (2015) Distal-to-proximal remodeling of small airway epithelium in smokers mediated by EGF signaling in small airway basal progenitor cells. In: A19. Pathologic programming of airway epithelium. American Thoracic Society international conference abstracts, American Thoracic Society, p A1050Google Scholar
  57. Katoh S, Kaminuma O, Hiroi T, Mori A, Ohtomo T, Maeda S, Shimizu H, Obase Y, Oka M (2011) CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1, cells induced by antigen challenge in mice. Eur J Immunol 41:3198–3207PubMedCrossRefGoogle Scholar
  58. Klagas I, Goulet S, Karakiulakis G, Zhong J, Baraket M, Black JL, Papakonstantinou E, Roth M (2009) Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD. Eur Respir J 34:616–628PubMedCrossRefGoogle Scholar
  59. Koff JL, Shao MX, Ueki IF, Nadel JA (2008) Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol 294:L1068–L1075PubMedCrossRefGoogle Scholar
  60. Kosako H, Yoshida T, Matsumura F, Ishizaki T, Narumiya S, Inagaki M (2000) Rho-kinase/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin/radixin/moesin proteins at the cleavage furrow. Oncogene 19:6059–6064PubMedCrossRefGoogle Scholar
  61. Krieg J, Hunter T (1992) Identification of the two major epidermal growth factor-induced tyrosine phosphorylation sites in the microvillar core protein ezrin. J Biol Chem 267:19258–19265PubMedGoogle Scholar
  62. Kumar S, Lanckacker E, Dentener M, Bracke K, Provoost S, De Grove K, Brusselle G, Wouters E, Maes T, Joos G (2016) Aggravation of allergic airway inflammation by cigarette smoke in mice is CD44-dependent. PLoS One 11:e0151113PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lackie PM, Baker JE, Gunthert U, Holgate ST (1997) Expression of CD44 isoforms is increased in the airway epithelium of asthmatic subjects. Am J Respir Cell Mol Biol 16:14–22PubMedCrossRefGoogle Scholar
  64. Lambrecht BN, Hammad H (2015) The immunology of asthma. Nat Immunol 16:45–56PubMedCrossRefGoogle Scholar
  65. Lawrence EJ, Boucher E, Mandato CA (2016) Mitochondria-cytoskeleton associations in mammalian cytokinesis. Cell Div 11:3PubMedPubMedCentralCrossRefGoogle Scholar
  66. Leir SH, Holgate ST, Lackie PM (2003) Inflammatory cytokines can enhance CD44-mediated airway epithelial cell adhesion independently of CD44 expression. Am J Physiol Lung Cell Mol Physiol 285:L1305–L1311PubMedCrossRefGoogle Scholar
  67. Lin CC, Lin WN, Hou WC, Hsiao LD, Yang CM (2015) Endothelin-1 induces VCAM-1 expression-mediated inflammation via receptor tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 309:L211–L225PubMedCrossRefGoogle Scholar
  68. Ma L, Liu YP, Zhang XH, Xing LX, Wang JL, Geng CZ (2009) Effect of RhoA signaling transduction on expression of ezrin in breast cancer cell lines. Ai Zheng 28:108–111PubMedGoogle Scholar
  69. Ma L, Liu YP, Zhang XH, Geng CZ, Li ZH (2013) Relationship of RhoA signaling activity with ezrin expression and its significance in the prognosis for breast cancer patients. Chin Med J 126:242–247PubMedGoogle Scholar
  70. Mackay DJ, Esch F, Furthmayr H, Hall A (1997) 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 138:927–938PubMedPubMedCentralCrossRefGoogle Scholar
  71. Manhire-Heath R, Golenkina S, Saint R, Murray MJ (2013) Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila. Nat Commun 4:2790PubMedCrossRefGoogle Scholar
  72. Martin M, Simon-Assmann P, Kedinger M, Martin M, Mangeat P, Real FX, Fabre M (2006) DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin. Eur J Cell Biol 85:769–783PubMedCrossRefGoogle Scholar
  73. Martin-Villar E, Megias D, Castel S, Yurrita MM, Vilaro S, Quintanilla M (2006) Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition. J Cell Sci 119:4541–4553PubMedCrossRefGoogle Scholar
  74. McRobert EA, Gallicchio M, Jerums G, Cooper ME, Bach LA (2003) The amino-terminal domains of the ezrin, radixin, and moesin (ERM) proteins bind advanced glycation end products, an interaction that may play a role in the development of diabetic complications. J Biol Chem 278:25783–25789PubMedCrossRefGoogle Scholar
  75. Menager C, Vassy J, Doliger C, Legrand Y, Karniguian A (1999) Subcellular localization of RhoA and ezrin at membrane ruffles of human endothelial cells: differential role of collagen and fibronectin. Exp Cell Res 249:221–230PubMedCrossRefGoogle Scholar
  76. Miura S, Sato K, Kato-Negishi M, Teshima T, Takeuchi S (2015) Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6. Nat Commun 6:8871PubMedPubMedCentralCrossRefGoogle Scholar
  77. Mori T, Kitano K, Terawaki S, Maesaki R, Fukami Y, Hakoshima T (2008) Structural basis for CD44 recognition by ERM proteins. J Biol Chem 283:29602–29612PubMedPubMedCentralCrossRefGoogle Scholar
  78. Neisch AL, Fehon RG (2011) Ezrin, radixin and moesin: key regulators of membrane-cortex interactions and signaling. Curr Opin Cell Biol 23:377–382PubMedPubMedCentralCrossRefGoogle Scholar
  79. Nethe M, Hordijk PL (2010) The role of ubiquitylation and degradation in RhoGTPase signalling. J Cell Sci 123:4011–4018PubMedCrossRefGoogle Scholar
  80. Ng T, Parsons M, Hughes WE, Monypenny J, Zicha D, Gautreau A, Arpin M, Gschmeissner S, Verveer PJ, Bastiaens PI, Parker PJ (2001) Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility. EMBO J 20:2723–2741PubMedPubMedCentralCrossRefGoogle Scholar
  81. Nijhara R, van Hennik PB, Gignac ML, Kruhlak MJ, Hordijk PL, Delon J, Shaw S (2004) Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes. J Immunol 173:4985–4993PubMedCrossRefGoogle Scholar
  82. Noble PB, Pascoe CD, Lan B, Ito S, Kistemaker LE, Tatler AL, Pera T, Brook BS, Gosens R, West AR (2014) Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling. Pulm Pharmacol Ther 29:96–107PubMedCrossRefGoogle Scholar
  83. Oda Y, Aishima S, Morimatsu K, Hayashi A, Shindo K, Fujino M, Mizuuchi Y, Hattori M, Tanaka M, Oda Y (2013) Differential ezrin and phosphorylated ezrin expression profiles between pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and invasive ductal carcinoma of the pancreas. Hum Pathol 44:1487–1498PubMedCrossRefGoogle Scholar
  84. Pakkanen R, Hedman K, Turunen O, Wahlstrom T, Vaheri A (1987) Microvillus-specific Mr 75,000 plasma membrane protein of human choriocarcinoma cells. J Histochem Cytochem 35:809–816PubMedCrossRefGoogle Scholar
  85. Parlato S, Giammarioli AM, Logozzi M, Lozupone F, Matarrese P, Luciani F, Falchi M, Malorni W, Fais S (2000) 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 19:5123–5134PubMedPubMedCentralCrossRefGoogle Scholar
  86. Parnell E, Koschinski A, Zaccolo M, Cameron RT, Baillie GS, Baillie GL, Porter A, McElroy SP, Yarwood SJ (2015) Phosphorylation of ezrin on Thr567 is required for the synergistic activation of cell spreading by EPAC1 and protein kinase A in HEK293T cells. Biochim Biophys Acta 1853:1749–1758PubMedPubMedCentralCrossRefGoogle Scholar
  87. Perez OD, Kinoshita S, Hitoshi Y, Payan DG, Kitamura T, Nolan GP, Lorens JB (2002) Activation of the PKB/AKT pathway by ICAM-2. Immunity 16:51–65PubMedCrossRefGoogle Scholar
  88. Perez-Cornejo P, Gokhale A, Duran C, Cui Y, Xiao Q, Hartzell HC, Faundez V (2012) Anoctamin 1 (Tmem16A) Ca2+-activated chloride channel stoichiometrically interacts with an ezrin-radixin-moesin network. Proc Natl Acad Sci U S A 109:10376–10381PubMedPubMedCentralCrossRefGoogle Scholar
  89. Pidoux G, Tasken K (2015) Anchored PKA as a gatekeeper for gap junctions. Commun Integr Biol 8:e1057361PubMedPubMedCentralCrossRefGoogle Scholar
  90. Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4:33–45PubMedCrossRefGoogle Scholar
  91. Pore D, Bodo J, Danda A, Yan D, Phillips JG, Lindner D, Hill BT, Smith MR, Hsi ED, Gupta N (2015) Identification of ezrin-radixin-moesin proteins as novel regulators of pathogenic B-cell receptor signaling and tumor growth in diffuse large B-cell lymphoma. Leukemia 29:1857–1867PubMedPubMedCentralCrossRefGoogle Scholar
  92. Rebillard A, Jouan-Lanhouet S, Jouan E, Legembre P, Pizon M, Sergent O, Gilot D, Tekpli X, Lagadic-Gossmann D, Dimanche-Boitrel MT (2010) Cisplatin-induced apoptosis involves a Fas-ROCK-ezrin-dependent actin remodelling in human colon cancer cells. Eur J Cancer 46:1445–1455PubMedCrossRefGoogle Scholar
  93. Reczek D, Bretscher A (1998) 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 273:18452–18458PubMedCrossRefGoogle Scholar
  94. Ribas C, Penela P, Murga C, Salcedo A, Garcia-Hoz C, Jurado-Pueyo M, Aymerich I, Mayor F Jr (2007) The G protein-coupled receptor kinase (GRK) interactome: role of GRKs in GPCR regulation and signaling. Biochim Biophys Acta 1768:913–922PubMedCrossRefGoogle Scholar
  95. Roumier A, Olivo-Marin JC, Arpin M, Michel F, Martin M, Mangeat P, Acuto O, Dautry-Varsat A, Alcover A (2001) The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation. Immunity 15:715–728PubMedCrossRefGoogle Scholar
  96. Sagara J, Tsukita S, Yonemura S, Tsukita S, Kawai A (1995) Cellular actin-binding ezrin-radixin-moesin (ERM) family proteins are incorporated into the rabies virion and closely associated with viral envelope proteins in the cell. Virology 206:485–494PubMedCrossRefGoogle Scholar
  97. Saygideger-Kont Y, Minas TZ, Jones H, Hour S, Celik H, Temel I, Han J, Atabey N, Erkizan HV, Toretsky JA, Uren A (2016) Ezrin enhances EGFR signaling and modulates erlotinib sensitivity in non-small cell lung cancer cells. Neoplasia 18:111–120PubMedPubMedCentralCrossRefGoogle Scholar
  98. Schmieder S, Nagai M, Orlando RA, Takeda T, Farquhar MG (2004) Podocalyxin activates RhoA and induces actin reorganization through NHERF1 and ezrin in MDCK cells. J Am Soc Nephrol 15:2289–2298PubMedCrossRefGoogle Scholar
  99. Shaffer MH, Dupree RS, Zhu P, Saotome I, Schmidt RF, McClatchey AI, Freedman BD, Burkhardt JK (2009) Ezrin and moesin function together to promote T cell activation. J Immunol 182:1021–1032PubMedPubMedCentralCrossRefGoogle Scholar
  100. Sitaraman SV, Wang L, Wong M, Bruewer M, Hobert M, Yun CH, Merlin D, Madara JL (2002) The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and ezrin upon agonist stimulation. J Biol Chem 277:33188–33195PubMedCrossRefGoogle Scholar
  101. Soares MA, Cohen OD, Low YC, Sartor RA, Ellison T, Anil U, Anzai L, Chang JB, Saadeh PB, Rabbani PS, Ceradini DJ (2016) Restoration of Nrf2 signaling normalizes the regenerative niche. Diabetes 65:633–646PubMedCrossRefGoogle Scholar
  102. Song Y, Wong C, Chang DD (2000) Overexpression of wild-type RhoA produces growth arrest by disrupting actin cytoskeleton and microtubules. J Cell Biochem 80:229–240PubMedCrossRefGoogle Scholar
  103. Stokka AJ, Mosenden R, Ruppelt A, Lygren B, Tasken K (2010) The adaptor protein EBP50 is important for localization of the protein kinase A-ezrin complex in T-cells and the immunomodulating effect of cAMP. Biochem J 425:381–388CrossRefGoogle Scholar
  104. Sun F, Hug MJ, Lewarchik CM, Yun CH, Bradbury NA, Frizzell RA (2000) E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells. J Biol Chem 275:29539–29546PubMedCrossRefGoogle Scholar
  105. Sun H, Zhu Y, Pan H, Chen X, Balestrini JL, Lam TT, Kanyo JE, Eichmann A, Gulati M, Fares WH, Bai H, Feghali-Bostwick CA, Gan Y, Peng X, Moore MW, White ES, Sava P, Gonzalez AL, Cheng Y, Niklason LE, Herzog EL (2016) Netrin-1 regulates fibrocyte accumulation in the decellularized fibrotic sclerodermatous lung microenvironment and in bleomycin-induced pulmonary fibrosis. Arthritis Rheumatol 68:1251–1261PubMedPubMedCentralGoogle Scholar
  106. Takahashi K, Sasaki T, Mammoto A, Takaishi K, Kameyama T, Tsukita S, Takai Y (1997) Direct interaction of the Rho GDP dissociation inhibitor with ezrin/radixin/moesin initiates the activation of the Rho small G protein. J Biol Chem 272:23371–23375PubMedCrossRefGoogle Scholar
  107. Tang DD (2015) Critical role of actin-associated proteins in smooth muscle contraction, cell proliferation, airway hyperresponsiveness and airway remodeling. Respir Res 16:134PubMedPubMedCentralCrossRefGoogle Scholar
  108. Timothy NP, Elizabeth AO, Gina ED, Timothy DO (2016) The receptor for advanced glycation end-products mediates VCAM-1 expression in pulmonary endothelial cells: implications for asthma and allergic airway disease. In: D31. Novel mechanisms of allergy and airway inflammation. American Thoracic Society international conference abstracts, American Thoracic Society, p A6693Google Scholar
  109. Totsukawa G, Yamakita Y, Yamashiro S, Hartshorne DJ, Sasaki Y, Matsumura F (2000) Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J Cell Biol 150:797–806PubMedPubMedCentralCrossRefGoogle Scholar
  110. Tran Quang C, Gautreau A, Arpin M, Treisman R (2000) Ezrin function is required for ROCK-mediated fibroblast transformation by the Net and Dbl oncogenes. EMBO J 19:4565–4576PubMedPubMedCentralCrossRefGoogle Scholar
  111. Turunen O, Winqvist R, Pakkanen R, Grzeschik KH, Wahlstrom T, Vaheri A (1989) Cytovillin, a microvillar Mr 75,000 protein. cDNA sequence, prokaryotic expression, and chromosomal localization. J Biol Chem 264:16727–16732PubMedGoogle Scholar
  112. Ullrich SJ, Robinson EA, Appella E (1986) Characterization of a chemically homogeneous tumor antigen from a methylcholanthrene-induced sarcoma, Meth A. Mol Immunol 23:545–555PubMedCrossRefGoogle Scholar
  113. Vaheri A, Carpen O, Heiska L, Helander TS, Jaaskelainen J, Majander-Nordenswan P, Sainio M, Timonen T, Turunen O (1997) The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol 9:659–666PubMedCrossRefGoogle Scholar
  114. Vallée L (2000) ERM proteins: from cellular architecture to cell signaling. Biol Cell 92:305–316CrossRefGoogle Scholar
  115. Wang B, Means CK, Yang Y, Mamonova T, Bisello A, Altschuler DL, Scott JD, Friedman PA (2012) Ezrin-anchored protein kinase A coordinates phosphorylation-dependent disassembly of a NHERF1 ternary complex to regulate hormone-sensitive phosphate transport. J Biol Chem 287:24148–24163PubMedPubMedCentralCrossRefGoogle Scholar
  116. Wang Y, Lin Z, Sun L, Fan S, Huang Z, Zhang D, Yang Z, Li J, Chen W (2014) Akt/ezrin Tyr353/NF-kappaB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma. Br J Cancer 110:695–705PubMedCrossRefGoogle Scholar
  117. Watson RL, Buck J, Levin LR, Winger RC, Wang J, Arase H, Muller WA (2015) Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. J Exp Med 212:1021–1041PubMedPubMedCentralCrossRefGoogle Scholar
  118. Weinman EJ, Minkoff C, Shenolikar S (2000) Signal complex regulation of renal transport proteins: NHERF and regulation of NHE3 by PKA. Am J Physiol Renal Physiol 279:F393–F399PubMedCrossRefGoogle Scholar
  119. Xiao Y, Sun M, Zhan Z, Ye Y, Huang M, Zou Y, Liang L, Yang X, Xu H (2014) Increased phosphorylation of ezrin is associated with the migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Rheumatology 53:1291–1300PubMedCrossRefGoogle Scholar
  120. Yang HS, Hinds PW (2003) Increased ezrin expression and activation by CDK5 coincident with acquisition of the senescent phenotype. Mol Cell 11:1163–1176PubMedCrossRefGoogle Scholar
  121. Yang HS, Hinds PW (2006) Phosphorylation of ezrin by cyclin-dependent kinase 5 induces the release of Rho GDP dissociation inhibitor to inhibit Rac1 activity in senescent cells. Cancer Res 66:2708–2715PubMedCrossRefGoogle Scholar
  122. Yonemura S, Hirao M, Doi Y, Takahashi N, Kondo T, Tsukita S, Tsukita S (1998) 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 140:885–895PubMedPubMedCentralCrossRefGoogle Scholar
  123. Yonemura S, Matsui T, Tsukita S, Tsukita S (2002) Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin proteins: an essential role for polyphosphoinositides in vivo. J Cell Sci 115:2569–2580PubMedGoogle Scholar
  124. Yoshida S, Fukutomi T, Kimura T, Sakurai H, Hatano R, Yamamoto H, Mukaisho K, Hattori T, Sugihara H, Asano S (2016) Comprehensive proteome analysis of brush border membrane fraction of ileum of ezrin knockdown mice. Biomed Res 37:127–139PubMedCrossRefGoogle Scholar
  125. Youn JY, Wang T, Cai H (2009) An ezrin/calpain/PI3K/AMPK/eNOSs1179 signaling cascade mediating VEGF-dependent endothelial nitric oxide production. Circ Res 104:50–59PubMedCrossRefGoogle Scholar
  126. Zhou R, Cao X, Watson C, Miao Y, Guo Z, Forte JG, Yao X (2003) Characterization of protein kinase A-mediated phosphorylation of ezrin in gastric parietal cell activation. J Biol Chem 278:35651–35659PubMedCrossRefGoogle Scholar
  127. Zhu L, Zhou R, Mettler S, Wu T, Abbas A, Delaney J, Forte JG (2007) High turnover of ezrin T567 phosphorylation: conformation, activity, and cellular function. Am J Physiol Cell Physiol 293:C874–C884PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Laboratory of Molecular Biology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  2. 2.Department of Surgery, Center of Immunology and Inflammation, Rutgers-New Jersey Medical SchoolRutgers UniversityNewarkUSA

Personalised recommendations