Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members.

Takeuchi, Kosei; Sato, Nobuhiro; Kasahara, Hideko; Funayama, Noriko; Nagafuchi, Akira; Yonemura, Shigenobu; Tsukita, Shöichiro

doi:10.1083/jcb.125.6.1371

Cited by 321 publications

(300 citation statements)

References 34 publications

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“…ERM proteins control cell shape primarily by regulating membrane protrusions and cell-substrate adhesion. In epithelial cells ERM proteins are necessary for the formation of apical microvilli (12)(13)(14). In fibroblasts ERM proteins regulate the assembly of focal adhesions (15) and dynamic membrane protrusions, including filopodia and lamellipodia (16,17).…”

mentioning

confidence: 99%

The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors

Baumgärtner

Sillman²,

Blackwood³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

125

150

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The mammalian Ste20-like Nck-interacting kinase (NIK) and its orthologs Misshapen in Drosophila and Mig-15 in Caenorhabditis elegans have a conserved function in regulating cell morphology, although through poorly understood mechanisms. We report two previously unrecognized actions of NIK: regulation of lamellipodium formation by growth factors and phosphorylation of the ERM proteins ezrin, radixin, and moesin. ERM proteins regulate cell morphology and plasma membrane dynamics by reversibly anchoring actin filaments to integral plasma membrane proteins. In vitro assays show that NIK interacts directly with ERM proteins, binding their N termini and phosphorylating a conserved C-terminal threonine. In cells, NIK and phosphorylated ERM proteins localize at the distal margins of lamellipodia, and NIK activity is necessary for phosphorylation of ERM proteins induced by EGF and PDGF, but not by thrombin. Lamellipodium extension in response to growth factors is inhibited in cells expressing a kinase-inactive NIK, suppressed for NIK expression with siRNA oligonucleotides, or expressing ezrin T567A that cannot be phosphorylated. These data suggest that direct phosphorylation of ERM proteins by NIK constitutes a signaling mechanism controlling growth factor-induced membrane protrusion and cell morphology.ezrin ͉ moesin ͉ ste20 kinase ͉ membrane protrusion T he Nck-interacting kinase (NIK) is a member of the germinal center kinase subfamily of Ste20͞MAP4K serine͞threonine kinases (1). Closely related to NIK are the mammalian kinases TNIK (2), MINK (3), and NRK͞NESK (4) and orthologs Misshapen (Msn) in Drosophila (5) and MIG-15 in Caenorhabditis elegans (6). NIK and its orthologs share a common function in regulating cell shape and migration. In mice, homozygous knockout of NIK results in early embryonic lethality with defects in mesoderm migration (7), and expression of kinase-inactive NIK attenuates epithelial cell invasion (8). Msn functions in determining epithelial polarity, dorsal closure. and neuronal targeting (5, 9, 10), and MIG-15 controls axonal navigation (6). NIK (1) and Msn (5) also share a conserved activation of the JNK pathway. NIK, however, does not directly phosphorylate JNK, nor do NIK nullizygous embryos precisely phenocopy mice lacking JNK1 or JNK2 (7). Additionally, activation of JNK is not associated with dynamic changes in cell morphology. Hence, NIK substrates that control cell morphogenesis have not been identified.We now report that the ERM proteins ezrin, radixin, and moesin are substrates for NIK. ERM proteins regulate cell morphology by cross-linking actin filaments to the plasma membrane. The N-terminal FERM (4.1 ERM) domain of ERM proteins binds to integral plasma membrane proteins and the C terminus binds F-actin (11). ERM proteins control cell shape primarily by regulating membrane protrusions and cell-substrate adhesion. In epithelial cells ERM proteins are necessary for the formation of apical microvilli (12)(13)(14). In fibroblasts ERM proteins regulate the assembly of focal adhesions (...

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mentioning

confidence: 99%

The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors

Baumgärtner

Sillman²,

Blackwood³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

125

150

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“…ERM proteins are localized at the plasma membrane in actin-rich surface structures (Fig 1) [5], such as microvilli, membrane ruffles, and lamellipodia in gut cells, lymphocytes, hepatocytes, spermatozoids, fibroblasts and in a variety of other cell types [5][6][7][8][9]. They are involved in various physiological processes including establishment of cell polarity, cell motility and cell signaling [10].…”

Section: General Overview Of Erm Proteins (Ezrin Radixin Moesin)mentioning

confidence: 99%

Model membranes to shed light on the biochemical and physical properties of ezrin/radixin/moesin

2013

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Ezrin, radixin and moesin (ERM) proteins are now more and more recognized to play a key role in a large number of important physiological processes such as morphogenesis, cancer metastasis and virus infection. Several recent reviews extensively discuss their biological functions [1][2][3][4]. In this review, we will first remind the main features of this family of proteins, which are now known as linkers and regulators of the plasma membrane/cytoskeleton linkage. We will then briefly review their implication in pathological processes such as cancer and viral infection. In a second part, we will focus on biochemical and biophysical approaches to study ERM interaction with lipid membranes and conformational change in well-defined environments. In vitro studies using biomimetic lipid membranes, especially large unilamellar vesicles (LUVs), giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) and recombinant proteins help to understand the molecular mechanism of conformational activation of ERM proteins. These tools are aimed to decorticate the different steps of the interaction, to simplify the experiments performed in vivo in much more complex biological environments. KeywordsEzrin; radixin and moesin; biomimetic membranes; phosphoinositol (4,5)-bisphosphate (PIP 2 ); large unilamellar vesicles; supported lipid bilayers; giant unilamelar vesicles Corresponding author: Catherine Picart, CNRS UMR 5628 (LMGP), Grenoble Institute of Technology and CNRS, 3 parvis Louis Néel, F-38016 Grenoble Cedex, France. Europe PMC Funders GroupAuthor Manuscript Biochimie. Author manuscript; available in PMC 2014 July 28. Published in final edited form as:Biochimie. 2013 January ; 95(1): 3-11. doi:10.1016/j.biochi.2012.09.033. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts Biological importance of Ezrin, Radixin and Moesin General overview of ERM proteins (Ezrin, Radixin, Moesin)ERM proteins are localized at the plasma membrane in actin-rich surface structures (Fig 1) [5], such as microvilli, membrane ruffles, and lamellipodia in gut cells, lymphocytes, hepatocytes, spermatozoids, fibroblasts and in a variety of other cell types [5][6][7][8][9]. They are involved in various physiological processes including establishment of cell polarity, cell motility and cell signaling [10]. They act as linkers between the plasma membrane and the cortical actin cytoskeleton. From a structural point of view, ERMs are constituted of 3 domains : a membrane binding domain, also known as FERM (for band 4.1 protein, ezrin, radixin and moesin), and intermediary region and a actin binding domain called C-ERMAD (for C-terminal ERM-association domain) (Fig 2A).The FERM domain, constituted of ~300 amino acids, is characteristic of the proteins of the band 4.1 superfamily. These proteins also present other types of domains, including PDZ, tyrosine phosphatase, SH2-like, tyrosine kinase, kinase-like, myosin head, and PH domains [11]. In ERM proteins, the FERM domain is followed by a long α-helical region, whi...

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“…The suppression of ERM expression by antisense oligonucleotides in thymoma cells as well as in mouse epithelial cells leads to the destruction of both cell-cell and cell-substrate adhesion [22] . Overexpression of ezrin in insect cells enhances cell adhesion [24] .…”

Section: Cell-substrate and Cell-cell Adhesionmentioning

confidence: 99%

“…More recently, several functional analyses demonstrated that they are involved in membrane structures formation. When thymoma cells are cultured in presence of antisense oligonucleotides, which suppress the expression of the three ERM, microvilli disappear from the cell surface [22] . A treatment of primary retinal pigment epithelium (PRE) culture with ezrin antisense oligonucleotides caused complete disappearance of apical microvilli [23] .…”

Section: Erm: Functional Insight: 81 Formation Of Cell Surfacementioning

confidence: 99%

Ezrin, Radixin and Moesin: Minor Molecule with Major Impact: A Review

Agarwal¹

2013

IOSR-JDMS

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Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members.

Cited by 321 publications

References 34 publications

The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors

The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors

Model membranes to shed light on the biochemical and physical properties of ezrin/radixin/moesin

Ezrin, Radixin and Moesin: Minor Molecule with Major Impact: A Review

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