Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor–mediated lipid raft dynamics

Gupta, Neetu; Wollscheid, Bernd; Watts, Julian D.; Scheer, Barbara; Aebersold, Ruedi; DeFranco, Anthony L.

doi:10.1038/ni1337

Cited by 187 publications

(237 citation statements)

References 41 publications

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“…Ezrin is present in a phosphorylated form in cells before stimulation through Fas, antigen receptors or chemokine receptors, and is dephosphorylated after these stimulations (Kondo et al, 1997;Delon et al, 2001;Brown et al, 2003;Faure et al, 2004;Gupta et al, 2006;Hao et al, 2009). Our observation that ezrin was dephosphorylated after FasL stimulation in T cells (Figure 1c) is in accordance with those reports.…”

Section: Discussionsupporting

confidence: 92%

“…Activated ezrin and moesin are required for the formation of the distal pole complex (Allenspach et al, 2001) and for the movement of a cytotoxic cell to target cells (Mrass et al, 2008). Alternatively, lymphocyte activation and remolding involves ezrin/moesin inactivation and dissociation from cortical actin (Delon et al, 2001;Brown et al, 2003;Faure et al, 2004;Gupta et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Ezrin is a negative regulator of death receptor-induced apoptosis

et al. 2009

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Ezrin links cortical actin filaments with the cell membrane, and has a critical role in many membrane-initiated events. Fas is directly associated with ezrin, but conflicting results have been reported for the involvement of ezrin in Fas-induced cell death. In this study we show that ezrin was associated with Fas in T cells before stimulation and was released shortly after Fas ligand (FasL) engagement. The knockdown of ezrin moderately increased Fastriggered or tumor necrosis factor-related apoptosisinducing ligand (TRAIL)-triggered cell death in normal T lymphocytes and in H9 cells, but had no effect on death receptor-induced apoptosis in type II cells, such as Jurkat and CEM. Expression of a dominant-negative form of ezrin also led to an increased Fas-induced apoptosis in H9 cells. Ezrin deficiency did not affect the internalization of Fas after Fas ligation. Instead, an enhanced formation of death-inducing signaling complex (DISC) was observed in H9 cells with ezrin knockdown, leading to accelerated caspase-8 activation. Together, our results suggest that ezrin has a negative role in the recruitment of Fas into signaling complexes in type I T cells. Loss of ezrin likely removes the constraint imposed by ezrin and facilitates the assembly of death receptor complex in T cells.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Ezrin is a negative regulator of death receptor-induced apoptosis

et al. 2009

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“…We employed a reverse genetic approach to investigate a role of these proteins in PAMP-induced defense responses and discovered three novel components of plant innate immunity. Using a similar quantitative proteomic approach on DRMs, a new player in human B-lymphocyte signaling was previously identified (41). Likewise, stimulus-induced changes in the plant DRM proteome were reported (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

PAMP (Pathogen-associated Molecular Pattern)-induced Changes in Plasma Membrane Compartmentalization Reveal Novel Components of Plant Immunity

Keinath

Kierszniowska

Lorek

et al. 2010

Journal of Biological Chemistry

281

252

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Plasma membrane compartmentalization spatiotemporally regulates cell-autonomous immune signaling in animal cells. To elucidate immediate early protein dynamics at the plant plasma membrane in response to the bacterial pathogen-associated molecular pattern (PAMP) flagellin (flg22) we employed quantitative mass spectrometric analysis on detergent-resistant membranes (DRMs) of Arabidopsis thaliana suspension cells. This approach revealed rapid and profound changes in DRM protein composition following PAMP treatment, prominently affecting proton ATPases and receptor-like kinases, including the flagellin receptor FLS2. We employed reverse genetics to address a potential contribution of a subset of these proteins in flg22-triggered cellular responses. Mutants of three candidates (DET3, AHA1, FER) exhibited a conspicuous defect in the PAMP-triggered accumulation of reactive oxygen species. In addition, these mutants showed altered mitogen-activated protein kinase (MAPK) activation, a defect in PAMP-triggered stomatal closure as well as altered bacterial infection phenotypes, which revealed three novel players in elicitor-dependent oxidative burst control and innate immunity. Our data provide evidence for dynamic elicitor-induced changes in the membrane compartmentalization of PAMP signaling components.To cope with the great number of potential pathogens, plants evolved specialized pattern recognition receptors (PRRs) 5 through which they detect pathogen-associated molecular patterns (PAMPs) at the cell surface (1). Within seconds to minutes after PAMP perception manifold intracellular responses occur, including ion fluxes across the plasma membrane (PM), increase of cytosolic Ca 2ϩ levels, production of reactive oxygen species (ROS) and protein phosphorylation. At later time points profound transcriptional changes, stomatal closure as well as local cell wall reinforcement take place (2).The best characterized plant PAMP perception system is the recognition of bacterial flagellin and its elicitor-active epitope, flg22, by the Arabidopsis PRR FLS2 (flagellin sensitive 2; (2)). FLS2 undergoes flg22-induced complex formation with BRl1-associated receptor kinase 1 (BAK1), which precedes and is required for FLS2 endocytosis (2, 3). Indeed, ligand-induced reduction in lateral membrane mobility of FLS2 has been observed in protoplasts (4), which could be explained by either ligand-dependent interactions of FLS2 with e.g. BAK1, the confinement of FLS2 to less mobile membrane compartments, or a combination of both. To ensure adequate perception of PAMPs and tightly regulated downstream signaling, the PM must be spatially highly organized and dynamic. In this context, the recruitment of FLS2 to specialized membrane domains seems crucial to enable ligand-induced endocytosis (5).During the past years, lateral compartmentalization has become a well-recognized topic in plant membrane research (6). The membrane raft hypothesis provides a plausible explanation for the spatial and temporal organization of biological membranes based on t...

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“…Antigen-induced BCR signalling leads to the transient dephosphorylation of ezrin 103 , which releases the plasma membrane from cortical actin and temporarily increases BCR diffusion, promoting BCR clustering 104 . After BCR microclusters form, ezrin is rephosphorylated around them, resulting in corralling by the surrounding actin and stabilization of their signalling (Fig.…”

Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

125

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor–mediated lipid raft dynamics

Cited by 187 publications

References 41 publications

Ezrin is a negative regulator of death receptor-induced apoptosis

Ezrin is a negative regulator of death receptor-induced apoptosis

PAMP (Pathogen-associated Molecular Pattern)-induced Changes in Plasma Membrane Compartmentalization Reveal Novel Components of Plant Immunity

Cytoskeletal control of B cell responses to antigens

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