Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain

Shcherbina, Anna; Bretscher, Anthony; Kenney, Dianne M.; Remold‐O′Donnell, Eileen

doi:10.1016/s0014-5793(98)01674-3

Cited by 110 publications

(101 citation statements)

References 35 publications

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“…Calpain proteolysis of ezrin with associated cytoskeletal changes has been demonstrated in endothelial cells, lymphocytes, neutrophils, NIH-3T3 cells, renal proximal tubule cells and gastric parietal cells Ariyoshi et al, 2001;Chen et al, 1994;Potter et al, 1998;Shcherbina et al, 1999;Yao et al, 1993). Ezrin co-localized with acetylated α-tubulin, a marker of ciliated cells, in the pulmonary epithelium.…”

Section: Discussionmentioning

confidence: 98%

“…At other times, however, stability of the cytoskeleton is necessary for normal cell function. By inhibiting the calpain-mediated proteolysis of cytoskeletal components, such as ezrin, calpastatin contributes to cytoskeleton stability Ariyoshi et al, 2001;Chen et al, 1994;Potter et al, 1998;Shcherbina et al, 1999). Maintaining cytoskeleton stability would be essential to the normal differentiation of ciliated epithelial cells during lung development.…”

Section: Discussionmentioning

confidence: 99%

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Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells

Gomperts

Gong-Cooper

Hackett

2004

Journal of Cell Science

125

102

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The forkhead box transcription factor Foxj1 is required for cilia formation and left-right axis determination. To define the role of Foxj1 in ciliogenesis, microarray analysis was performed to identify differentially expressed genes in the pulmonary epithelium of foxj1 +/+ and foxj1 -/-mice. In the absence of Foxj1, the expression of calpastatin, an inhibitor of the protease calpain, decreased. RNase protection confirmed the decrease in calpastatin expression and decreased calpastatin was detected in the proximal pulmonary epithelium of foxj1 -/-mice by immunohistochemistry. No change was detected in the expression of calpain 2 in the pulmonary epithelium by western blot or immunohistochemistry. By western blot and immunofluorescence, ezrin, a substrate for calpain, was also found to decrease in the pulmonary epithelium of foxj1 -/-mice. No change in ezrin gene expression was found by RT-PCR. A decrease in ezrin binding phosphoprotein-50 (EBP-50) was also detected by immunofluorescence in the foxj1 -/-mouse pulmonary epithelium. Immunoelectron microscopy demonstrated ezrin associated with the basal bodies of cilia in the pulmonary epithelium. Treatment of tracheal explants from foxj1 -/-mice with a calpain inhibitor resulted in a partial reappearance of cilia observed in these mice. Additionally, following treatment of foxj1 -/-tracheal explants with calpain inhibitor, basal bodies were observed in an apical location along with relocalization of ezrin and EBP-50. Regulation of calpain activity by calpastatin thus provides a mechanism for regulating the anchoring of basal bodies to the apical cytoskeleton in ciliated cells. In the absence of Foxj1, decreased calpastatin expression with decreased ezrin and EBP-50 results in an inability of basal bodies to anchor to the apical cytoskeleton and subsequent failure of axonemal formation.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells

Gomperts

Gong-Cooper

Hackett

2004

Journal of Cell Science

125

102

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“…Expression of the dominant-negative N-terminus of ezrin strongly inhibited migration and metastasis of human melanoma cells (Federici et al, 2009), and in many tumour types ezrin dysregulation has been implicated in tumour progression and metastasis (Elliott et al, 2004; Endo et al., 2009;Khanna et al, 2004;Makitie et al, 2001;Ren et al, 2009;Weng et al, 2005;Yu et al, 2004). Although ezrin and moesin are highly homologous and might act redundantly in many processes, they have specific cellular functions, undergo different regulation mechanisms and show different expression patterns (Ilani et al, 2007;Shaffer et al, 2009;Shcherbina et al, 1999). Therefore, it would interesting to assess the involvement of moesin in the movement of blebbing amoeboid cells in order to understand whether ezrin and moesin functions act redundantly of each other or whether ezrin is specifically important.…”

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confidence: 99%

An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells

Lorentzen

Bamber

Sadok

et al. 2011

Journal of Cell Science

109

111

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SummaryMelanoma cells can switch between an elongated mesenchymal-type and a rounded amoeboid-type migration mode. The rounded 'amoeboid' form of cell movement is driven by actomyosin contractility resulting in membrane blebbing. Unlike elongated A375 melanoma cells, rounded A375 cells do not display any obvious morphological front-back polarisation, although polarisation is thought to be a prerequisite for cell movement. We show that blebbing A375 cells are polarised, with ezrin (a linker between the plasma membrane and actin cytoskeleton), F-actin, myosin light chain, plasma membrane, phosphatidylinositol (4,5)-bisphosphate and b1-integrin accumulating at the cell rear in a uropod-like structure. This structure does not have the typical protruding shape of classical leukocyte uropods, but, as for those structures, it is regulated by protein kinase C. We show that the ezrin-rich uropod-like structure (ERULS) is an inherent feature of polarised A375 cells and not a consequence of cell migration, and is necessary for cell invasion. Furthermore, we demonstrate that membrane blebbing is reduced at this site, leading to a model in which the rigid ezrin-containing structure determines the direction of a moving cell through localised inhibition of membrane blebbing. Journal of Cell ScienceIn confined spaces, blebbing cells can move forward without adhesion by a process termed 'chimneying' (Hawkins et al., 2009;Malawista and de Boisfleury Chevance, 1997). In fibrillar threedimensional matrices, such as collagen gels, blebs can expand into pores in the matrix, causing the squeezing phenotype observed in amoeboid lymphocytes and cancer cells in collagen gels (Haston and Shields, 1984;Wolf et al., 2003a). Cells that form small blebs can use them to 'elbow' their way through the meshwork of the ECM (Friedl and Wolf, 2009). The site of bleb formation determines the direction of cell movement (Keller and Bebie, 1996). However, some cells, such as A375 melanoma cells, form multiple blebs over the membrane and would therefore not be able to move directionally. However, A375 melanoma cells are able to invade into a collagen matrix and move in vitro and in vivo (Sahai and Marshall, 2003;Sanz-Moreno et al., 2008). As asymmetry is a prerequisite of cell movement (Petrie et al., 2009), this suggests some form of cellular polarisation. To understand cell movement driven by multiple blebs, we investigated polarisation in blebbing 'amoeboid' A375 melanoma cells. We show that A375 cells form an ezrin-rich uropod-like structure (which we call the ERULS) at their cell rear, and that this is required for invasion into a three-dimensional matrix. We present a model whereby accumulation of ezrin, membrane and actin in this structure reflects strong connections between the plasma membrane and the submembrane cortex, leading to the formation of a rigid structure that inhibits blebbing at the back of the cell. This leads to net movement of the cell in the direction opposite to the uropod-like structure. Our model explains how cells can move ...

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“…The degradation of ezrin leads to a disruption of the actin cytoskeleton. However, moesin and radixin are resistant to calpain [11] . In their nonphosphorylated state ERM proteins are present as monomers and have no site available for interaction with other molecules due to the intramolecular interaction.…”

Section: Inactivation Of Erm Proteinsmentioning

confidence: 99%

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

Agarwal¹

2013

IOSR-JDMS

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Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain

Cited by 110 publications

References 35 publications

Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells

Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells

An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells

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

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