ERM proteins: From cellular architecture to cell signaling

Louvet-Vallée, Sophie

doi:10.1016/s0248-4900(00)01078-9

Cited by 285 publications

(252 citation statements)

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“…We discovered that Sic specifically binds ezrin and moesin, two members of the ERM family of proteins that also includes radixin, erythrocyte band 4.1 protein, and merlin͞schwannomin (the neurofibromatosis type 2 protein) (13). These proteins are concentrated in specialized membrane structures such as microvilli, filopodia, and lamellipodia, and participate in the formation of these structures through the creation of plasma membrane͞actin filament linkages (13,17). Sic entered A549 cells very rapidly, Sic1.01 for 5 min, fixed, and permeabilized.…”

Section: Discussionmentioning

confidence: 99%

“…Ezrin and moesin mediate the interaction of the actinbased cytoskeleton with the plasma membrane and thus participate in formation of cellular protrusions and cell motility (13,17). In PMNs, ezrin and moesin localize to the cytoplasmic surface of the plasma membrane and are present at the posterior pole or uropod of migrating cells (18,19).…”

Section: Increased Phagocytosis and Killing Of The Sic Mutant Strain mentioning

confidence: 99%

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Insight into the molecular basis of pathogen abundance: Group AStreptococcusinhibitor of complement inhibits bacterial adherence and internalization into human cells

Hoe

Ireland

DeLeo

et al. 2002

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

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Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption͞ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics. microbiology ͉ Serotype M1 ͉ epidemic waves ͉ ezrin F or most bacterial pathogens, there is relatively little understanding of why certain clonally related isolates cause abundant infections, whereas others do not. Molecular explanation of these phenomena is critical to development of rational methods to limit pathogen emergence, resurgence, and dissemination.Group A Streptococcus (GAS) is an important human pathogen that causes infections ranging from pharyngitis to necrotizing fasciitis and the postinfectious sequelae acute rheumatic fever and acute glomerulonephritis. GAS are genetically highly heterogeneous. For example, more than 150 distinct M-types have been identified on the basis of antigenic differences in the M protein, an antiphagocytic surface molecule that is an important virulence factor (1). However, GAS expressing relatively few M types cause the majority of human invasive infections. In particular, M1 strains are the most common serotype recovered from invasive disease episodes and also have a propensity to cause epidemics (2).Streptococcal inhibitor of complement (Sic) is a secreted protein produced by serotype M1 GAS that inhibits the formation of the membrane attack complex (MAC) of complement in vitro by binding to the C5b-C7 complex (3, 4). Sic production is necessary for per...

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Section: Discussionmentioning

confidence: 99%

Section: Increased Phagocytosis and Killing Of The Sic Mutant Strain mentioning

confidence: 99%

Insight into the molecular basis of pathogen abundance: Group AStreptococcusinhibitor of complement inhibits bacterial adherence and internalization into human cells

Hoe

Ireland

DeLeo

et al. 2002

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

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“…By inhibitory self-association through intra-or intermolecular head-to-tail interactions between the NT and CT domains, several active binding sites on ERM proteins are masked. The activation process, a conformational change of the protein structure, is tightly regulated by the phosphorylation of a conserved threonine residue in the CT domain of each ERM protein (Louvet-Vallee, 2000). This phosphorylation is an important step in ERM protein activation, which disrupts the intramolecular interaction.…”

Section: Introductionmentioning

confidence: 99%

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

et al. 2011

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Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.

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“…It connects NHERF/EBP-50 (which in turn binds important membrane proteins such as CFTR and NHE-3) to F-actin and also enables protein kinase A-mediated regulation of apical channels (Kurashima et al, 1999;Louvet-Vallée, 2000;Weinman et al, 2000Weinman et al, , 2001. Because ezrin is the earliest protein of this complex scaffold to be recruited, it has long been considered as an organizer of the brush border (Bretscher et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Intermediate Filaments Interact with Dormant Ezrin in Intestinal Epithelial Cells

Wald

Oriolo

Casanova

et al. 2005

MBoC

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Ezrin connects the apical F-actin scaffold to membrane proteins in the apical brush border of intestinal epithelial cells. Yet, the mechanisms that recruit ezrin to the apical domain remain obscure. Using stable CACO-2 transfectants expressing keratin 8 (K8) antisense RNA under a tetracycline-responsive element, we showed that the actin-ezrin scaffold cannot assemble in the absence of intermediate filaments (IFs). Overexpression of ezrin partially rescued this phenotype. Overexpression of K8 in mice also disrupted the assembly of the brush border, but ezrin distributed away from the apical membrane in spots along supernumerary IFs. In cytochalasin D-treated cells ezrin localized to a subapical compartment and coimmunoprecipitated with IFs. Overexpression of ezrin in undifferentiated cells showed a Triton-insoluble ezrin compartment negative for phospho-T567 (dormant) ezrin visualized as spots along IFs. Pulse-chase analysis showed that Triton-insoluble, newly synthesized ezrin transiently coimmunoprecipitates with IFs during the first 30 min of the chase. Dormant, but not active (p-T567), ezrin bound in vitro to isolated denatured keratins in Far-Western analysis and to native IFs in pull-down assays. We conclude that a transient association to IFs is an early step in the polarized assembly of apical ezrin in intestinal epithelial cells. INTRODUCTIONEzrin, a member of the ezrin-radixin-moesin (ERM) family, is a conspicuous component of the apical F-actin-based scaffold in simple epithelial cells. It connects NHERF/EBP-50 (which in turn binds important membrane proteins such as CFTR and NHE-3) to F-actin and also enables protein kinase A-mediated regulation of apical channels (Kurashima et al., 1999;Louvet-Vallée, 2000;Weinman et al., 2000Weinman et al., , 2001. Because ezrin is the earliest protein of this complex scaffold to be recruited, it has long been considered as an organizer of the brush border (Bretscher et al., 1997). In support of that view, ezrin knockout mice show a distinctive brush-border phenotype with much shorter microvilli that resemble undifferentiated stages (Saotome et al., 2004). Furthermore, expression of ezrin in fibroblasts is sufficient to organize microvilli (Shaw et al., 1998). After translation, ezrin initially adopts a "dormant" configuration, in which the C-and N-terminal domains bind to each other. On phosphorylation in T567, it changes to an open "active" configuration, freeing the C-terminal domain (C-ERMAND) to bind F-actin and the N-terminal domain (N-ERMAND) to bind NHERF or transmembrane proteins (Bretscher et al., 2000). Although the mechanism of activation and assembly of ezrin has been studied in great detail by several groups, the mechanisms that ensure that ezrin assembly occur mostly under the apical membrane of simple epithelial cells remain obscure. Fievet et al. (2004) have shown that binding to phosphatidylinositol 4,5-diphosphate (PIP 2 ) is a prerequisite for activation. However, PIP 2 is not known to be apically polarized in epithelial cells, rather it is basol...

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ERM proteins: From cellular architecture to cell signaling

Cited by 285 publications

References 88 publications

Insight into the molecular basis of pathogen abundance: Group AStreptococcusinhibitor of complement inhibits bacterial adherence and internalization into human cells

Insight into the molecular basis of pathogen abundance: Group AStreptococcusinhibitor of complement inhibits bacterial adherence and internalization into human cells

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

Intermediate Filaments Interact with Dormant Ezrin in Intestinal Epithelial Cells

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