Roles of p-ERM and Rho–ROCK signaling in lymphocyte polarity and uropod formation

Lee, Jong‐Hwan; Katakai, Tomoya; Hara, Takahiro; Gonda, Hiroyuki; Sugai, Manabu; Shimizu, Akira

doi:10.1083/jcb.200403091

Cited by 167 publications

(195 citation statements)

References 36 publications

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“…Moreover, cells expressing NT moesin showed remarkably diminished migration, indicating that the N-terminal domain alone acts in a dominant-negative manner to inhibit the endogenous ERM proteins by competing for the binding of membrane proteins. These results obtained in melanoma cells are consistent with previous observations for the functions of moesin in mediating cytoskeleton rearrangement and modulating cell migrations (Lee et al, 2004).…”

Section: Cd146 Interacts With Erm In Cell Migrationsupporting

confidence: 93%

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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Section: Cd146 Interacts With Erm In Cell Migrationsupporting

confidence: 93%

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

et al. 2011

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“…Activated ERM proteins associate with CD44 and ligate CD44 to F-actin [17,18] such that CD44 becomes enriched in the uropod of migrating cells [20], whereas CD49d is recovered from the uropod and the leading lamella [53]. However, in AA LNC, co-localization of ezrin with CD44 was seen in the uropod and also along the cell body as well as weakly in the leading lamella.…”

Section: The Cd44-cd49d Association Influences Leukocyte Migrationmentioning

confidence: 99%

“…The cytoplasmic tail of CD44 associates with ERM (Ezrin, Radixin, Moesin) proteins [16,17]. Activated ERM proteins cross-link transmembrane proteins to the actin cytoskeleton [17,18], that supports lymphocyte polarization [19,20]. Notably too, CD44 is constitutively associated with lck, lyn and fyn [21][22][23], Src family protein tyrosine kinases (PTK) important in leukocyte activation.…”

Section: Introductionmentioning

confidence: 99%

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

2006

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CD44 is involved in leukocyte migration and activation and has recently been reported to contribute to leukocyte extravasation by associating with CD49d. We explored whether similar changes in CD44 activity are seen in vivo using murine alopecia areata (AA) as a chronic, organ‐related autoimmune disease model system. Expression of the activated, hyaluronan‐binding form of CD44, and of CD49d, was elevated in draining lymph node cells (LNC) of AA‐affected mice as compared to control mice. LNC of AA mice displayed increased motility, proliferative activity and apoptosis resistance, which were equally well inhibited by anti‐CD44 and anti‐CD49d. The latter is the sequelae of the association between CD44 and CD49d that is seen in activated lymphocytes. Significantly, due to CD44‐CD49d complex formation, CD44 gains access to focal adhesion kinase and CD49d gains access to CD44‐associated lck and ezrin, such that downstream kinases become activated via CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually avail themselves of the partner's signaling pathways and the ligand binding of each one triggers signaling pathways of both. This strongly influences the lymphocytes’ activation state and function.

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Section: Specificity Of the Interaction Between Erm And Phosphoinosidesmentioning

confidence: 99%

“…Low curvature membranes such as GUV and SLB are good mimics of flat plasma membrane regions. A parallel can then be drawn between ERM clustering at the GUVs or SLB surface and the formation of ERM-rich regions during cell migration [76], the establishment of the immune synapse [77] or the formation of high curvature blebs [78], where spatial distribution of PIP 2 may also be altered.ERMs are also associated to positive curvature membranes of various internal compartments. For instance, ezrin was recently shown to play a role in maturation of endosomes [79], whereas moesin was shown to bind PIP 2 at the surface of clathrin-coated vesicles [80].…”

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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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Roles of p-ERM and Rho–ROCK signaling in lymphocyte polarity and uropod formation

Cited by 167 publications

References 36 publications

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

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

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

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

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