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The ERM (Ezrin, Radixin, Moesin) Actin-Binding Proteins 

A group of proteins including Ezrin, Radixin, Moesin, NF2-tumour suppressor (also known as Merlin), many of which are actin-binding proteins.  Some members of this group have an unusual ability to bind to discriminate between iso-forms of actin binding b- but not a-F-actin (Hirao et al, 1996).  In ezrin the actin binding region has been found to be contained in the C-terminus and similar regions are present in moesin, radixin, but not in merlin (Turunen et al, 1989, 1994).  
Structure of the ERM family.
A trick of the tail? 
The actin-binding region of ERM proteins reside in the tail.  Like vinculin, this actin-binding region is "hidden" in  the inactive state.  The actin-binding region has been localized to the last 34 amino-acids in the sequence of human ezrin (
Turunen et al, 1994; Smith et al, 2003)
Regulation by PIP2.
Like many actin-binding proteins, especially those with a cellular distribution close to the membrane, the ERM group are regulated by phosphoinositide lipids. 
Binding Partners
Regulation by Phosphorylation
Ezrin is a substrate for the Lck tyrosine kinase (
Autero et al, 2003).

References:-

Amieva, M. R., Litman, P., Huang, L., Ichimaru, E. & Furthmayr, H. (1999) Disruption of dynamic cell surface architecture of NIH3T3 fibroblasts by the N-terminal domains of moesin and ezrin: in vivo imaging with GFP fusion proteins., J.Cell Sci. 112, 111-125.

Autero, M., Heiska, L., Ronnstrand, L., Vaheri, A., Gahmerg, C. G. & Carpen, O. (2003) Ezrin is a substrate for Lck in T cells., FEBS Lett. 535, 82-86.

Brault, E., Gautreau, A., Lamarine, M., Callebaut, I., Thomas, G. & Goutebroze, L. (2001) 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.

Bretscher, A. (1999) Regulation of a cortical structure by the ezrin-radixin-moesin protein family, Curr.Op.Cell Biol. 11, 109-116.

Córdova, N. J., Ermentrout, B. & Oster, G. F. (1992) Dynamics of single-motor molecules: The thermal ratchet model, Proc.Nat.Acad.Sci.USA. 89, 339-343.

Edelstein-Keshet, L. & Ermentrout, G. B. (1990) Contact response of cells can mediate morphogenetic pattern formation, Differentiation. 45, 147-159.

Edwards, S. D. & Keep, N. H. (2001) The 2.7A crystal structure of the activated FERM domain of meosin: An analysis of structural changes on activation., Biochemistry. 40, 7061-7068.

Grönholm, M., Saino, M., Zhao, F., Heiska, L., Vaheri, A. & Carpén, O. (1999) Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin., J.Cell Sci. 112, 895-904.

Hamada, K., Shimizu, T., Matsui, T., Tsukita, S., Tsukita, S. & Hakoshima, T. (2000) Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain., EMBO J. 19, 4449-4462.

Han, B.-G., Nunomura, W., Takakuwa, Y., Mohandas, N. & Jap, B. J. (2000) Protein 4.1R core domain structure and insights into regulation of cytoskeleton organization., Nature. 7, 871-875.

Hirao, M., Sato, N., Kondo, T., Yonemura, S., Monden, M., Sasaki, T . et al  (1996). J.Cell Biol. 135, 37-51.

Hishiya, A., Ohnishi, M., Tamura, S. & Nakamura, F. (1999) Protein phosphatase 2C inactivates F-actin binding of human platelet moesin., J.Biol.Chem. 274, 26705-26712.

James, M., Manchanda, N., Gonzalez-Agosti, C., Hartwig, J. H. & Ramesh, V. (2001) 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.

Mangeat, P., Roy, C. & Martin, M. (1999) ERM proteins in cell adhesion and membrane dynamics, Trends Cell Biol. 9, 187-192.

Melendez-Vasquez, C. V., Rios, J., Zanazzi, G., Lambert, S., Bretscher, A. & Salzer, J. L. (2001) Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM) -positive Schwann cell processes., PNAS. 98, 1235-1240.

Neill, G. W. & Crompton, M. R. (2001) Binding of the merlin-1 product of the neuroblastomatosis type 2 tumour suppressor gene to a novel site in b-fodrin is regulated by association between merlin domains., Biochem. J. 358, 727-735.

Olsson, P.-A., Korhonen, L., Mercer, E. A. & Lindholm, D. (1999) MIR is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth., J.Biol.Chem. 274, 36288-36292.

Paglini, G., Kunda, P., Quiroga, S., Kosik, K. & Cáceres, A. (1998) Suppression of radixin and moesin alters growth cone morphology, motility, and process formation in primary cultured neurons., J.Cell Biol. 143, 443-455.

Schwienbacher, C., Magri, E., Trombetta, G. & Grazi, E. (1995) Osmotic properties of the calcium-regulated actin filament, Biochemistry. 34, 1090-1095.

Shaw, R. J., Henry, M., Solomon, F. & Jacks, T. (1998) Rho-dependent phosphorylation and relocalization of ERM proteins into apical membrane /actin protrusions in fibroblasts., Mol.Biol.Cell. 9, 403-419.

Smith, W. J., Nassar, N., Bretscher, A., Cerione, R. A. & Karplus, P. A. (2003) Structure of the Active N-terminal Domain of Ezrin. CONFORMATIONAL AND MOBILITY CHANGES IDENTIFY KEYSTONE INTERACTIONS, J. Biol. Chem. 278, 4949-4956.

Takeuchi, K., Kawashima, A., Nagafuchi, A. & Tsukita, S. (1994) Structural diversity of band 4.1 superfamily members, J.Cell Sci. 107, 1921-1928.

Terskikh, A., Fradkov, A., Ermakova, G., Zaraisky, A., Tan, P., Kajava, A. V., Zhao, X., Lukyanov, S., Matz, M., Kim, S., Weissman, I. & Siebert, P. (2000) "Fluorescent timer": Protein that changes color with time., Science. 290, 1585-1588.

Tsukita, S., Yonemura, S. & Tsukita, S. (1997) ERM (exrin/radixin/moesin) family: from cytoskeleton to signal transduction, Curr.Opin.Cell Biol. 9, 70-75.

Turunen, O., Winqvist, R., Pakkanen, R., Grzeschik, K.-H., Wahlstrom, T. & Vaheri, A. (1989) Cytovillin, a microvillar Mr 75,000 protein. cDNA sequence, prokaryotic expression, and chromosomal localization., J.Biol.Chem. 264, 16727-16732.

Turunen, O., Wahlstrom, T. & Vaheri, A. (1994) Ezrin has a COOH-terminal actin-binding site that is conserved in the Ezrin protein family., J.Cell Biol. 126, 1445-1453.

Yonemura, S., Hirao, M., Yoshinori, D., Takahashi, N., Kondo, T., Tsukita, S. & Tsukita, S. (1998) Ezrin/radixin/moesin (ERM) proteins bind to positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43 and ICAM-2., J.Cell Biol. 140, 885-895.

Yonemura, S., Tsukita, S. & Tsukita, S. (1999) Direct involvement of ezrin/radixin/moesin (ERM)-binding membrane proteins in the organisation of microvilli in collaboration with activated ERM proteins., J.Cell Biol. 145, 1497-1509.

 
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