Involvement of filamentous actin in setting the threshold for degranulation in mast cells

Tolarová, Helena; Dráberová, Lubica; Heneberg, Petr; Dráber, Petr

doi:10.1002/eji.200424991

Cited by 45 publications

(50 citation statements)

References 25 publications

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“…Thus the data indicate that the greater depolymerization of F-actin in NTAL À/À cells is not the main reason for their greater secretion. The bell-shaped secretory responses to increasing LB concentrations are compatible with the reported stimulatory effects of LB at low concentrations [15] and the inhibitory effects at higher concentrations [16].…”

Section: Drug-induced F-actin Depolymerization In Wt and Ntal à/à Cellssupporting

confidence: 83%

The transmembrane adaptor protein NTAL signals to mast cell cytoskeleton via the small GTPase Rho

et al. 2010

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The transmembrane adaptor protein NTAL (non-T-cell activation linker) participates in signalosome assembly in hematopoietic cells, but its exact role in cell physiology remains enigmatic. We report here that BM-derived mast cells from NTAL-deficient mice, responding to Ag alone or in combination with SCF, exhibit reduced spreading on fibronectin, enhanced filamentous actin depolymerization and enhanced migration towards Ag relative to WT cells. No such differences between WT and NTAL À/À BM-derived mast cells were observed when SCF alone was used as activator. We have examined the activities of two small GTPases, Rac and Rho, which are important regulators of actin polymerization. Stimulation with Ag and/or SCF enhanced activity of Rac(1,2,3) in both NTAL À/À and WT cells. In contrast, RhoA activity decreased and this trend was much faster and more extensive in NTAL À/À cells, indicating a positive regulatory role of NTAL in the recovery of RhoA activity. After restoring NTAL into NTAL À/À cells, both spreading and actin responses were rescued. This is the first report of a crucial role of NTAL in signaling, via RhoA, to mast cell cytoskeleton.

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Section: Drug-induced F-actin Depolymerization In Wt and Ntal à/à Cellssupporting

confidence: 83%

The transmembrane adaptor protein NTAL signals to mast cell cytoskeleton via the small GTPase Rho

et al. 2010

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“…Inhibition of actin polymerization leads to significant enhancement of the secretory response induced through FceRI [25] or Thy-1 [20]. Our finding that inhibitors of actin polymerization enhance FRET efficiency between FceRI and Thy-1.1 suggests that the decreased level of F-actin leads to loss of exclusion of the FceRI from Thy-1 in nonactivated cells.…”

Section: Cross-talk Between Thy-1 and Fcerimentioning

confidence: 73%

“…Biochemical studies with detergent-solubilized cells implied that FceRI-mediated activation is initiated by coalescence of aggregated FceRI with DRM [10,12] and that F-actin is involved in this process [19,20]. However, EM observations failed to discern any significant increase in association between Thy-1 and aggregated FceRI [12,15].…”

Section: Cross-talk Between Thy-1 and Fcerimentioning

confidence: 99%

Topography of plasma membrane microdomains and its consequences for mast cell signaling

et al. 2006

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Thy-1 (CD90) is a glycoprotein bound to the plasma membrane by a GPI anchor. Aggregation of Thy-1 in mast cells and basophils induces activation events independent of the expression of Fce receptor I (FceRI). Although we and others have previously suggested that plasma membrane microdomains called lipid rafts are implicated in both Thy-1 and FceRI signaling, properties of these microdomains are still poorly understood. In this study we used rat basophilic leukemia cells and their transfectants expressing both endogenous Thy-1.1 and exogenous Thy-1.2 genes and analyzed topography of the Thy-1 isoforms and Thy-1-induced signaling events. Light microscopy showed that both Thy-1 isoforms were in the plasma membrane distributed randomly and independently. Electron microscopy on isolated membrane sheets and fluorescence resonance energy transfer analysis indicated cross-talk between Thy-1 isoforms and between Thy-1 and FceRI. This cross-talk was dependent on actin filaments. Thy-1 aggregates colocalized with two transmembrane adaptor proteins, non-T cell activation linker (NTAL) and linker for activation of T cells (LAT), which had been shown to inhabit different membrane microdomains. Thy-1 aggregation led to tyrosine phosphorylation of these two adaptors. The combined data indicate that aggregated GPI-anchored proteins can attract different membrane proteins in different clusters and thus can trigger different signaling pathways.

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“…FcRI signaling also leads to recruitment of SH2 domain-containing phosphatase-2 (SHP2) (PTPN11) phosphatase to FcRI ␤-subunit (11), Gab2 adaptor protein (12), PECAM-1 (13,14), and MAFA (15). SHP2 interaction with these ligands likely contributes to activation of SHP2 phosphatase activity, which was previously reported following FcRI aggregation in mast cells (16,17). In RBL-2H3 rat mucosal mast cells, clustering of MAFA led to SHP2 recruitment and reduced Syk kinase activation (18), suggesting that Syk is a potential substrate of SHP2 following membrane recruitment and activation (3).…”

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confidence: 74%

SH2 Domain-Containing Phosphatase-2 Protein-Tyrosine Phosphatase Promotes FcεRI-Induced Activation of Fyn and Erk Pathways Leading to TNFα Release from Bone Marrow-Derived Mast Cells

McPherson

Sharma

Everingham

et al. 2009

The Journal of Immunology

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Clustering of the high affinity IgE receptor (FcεRI) in mast cells leads to degranulation and production of numerous cytokines and lipid mediators that promote allergic inflammation. Initiation of FcεRI signaling involves rapid tyrosine phosphorylation of FcεRI and membrane-localized adaptor proteins that recruit additional SH2 domain-containing proteins that dynamically regulate downstream signaling. SH2 domain-containing phosphatase-2 (SHP2) is a protein-tyrosine phosphatase implicated in FcεRI signaling, but whose function is not well defined. In this study, using a mouse model allowing temporal shp2 inactivation in bone marrow-derived mast cells (BMMCs), we provide insights into SHP2 functions in the FcεRI pathway. Although no overt defects in FcεRI-induced tyrosine phosphorylation were observed in SHP2 knock-out (KO) BMMCs, several proteins including Lyn and Syk kinases displayed extended phosphorylation kinetics compared with wild-type BMMCs. SHP2 was dispensable for FcεRI-induced degranulation of BMMCs, but was required for maximal activation of Erk and Jnk mitogen-activated protein kinases. SHP2 KO BMMCs displayed several phenotypes associated with reduced Fyn activity, including elevated phosphorylation of the inhibitory pY531 site in Fyn, impaired signaling to Grb2-associated binder 2, Akt/PKB, and IκB kinase, and decreased TNF-α release compared with control cells. This is likely due to elevated Lyn activity in SHP2 KO BMMCs, and the ability of Lyn to antagonize Fyn activity. Overall, our study identifies SHP2 as a positive effector of FcεRI-induced activation of Fyn/Grb2-associated binder 2/Akt and Ras/Erk pathways leading to TNF-α release from mast cells.

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Involvement of filamentous actin in setting the threshold for degranulation in mast cells

Cited by 45 publications

References 25 publications

The transmembrane adaptor protein NTAL signals to mast cell cytoskeleton via the small GTPase Rho

The transmembrane adaptor protein NTAL signals to mast cell cytoskeleton via the small GTPase Rho

Topography of plasma membrane microdomains and its consequences for mast cell signaling

SH2 Domain-Containing Phosphatase-2 Protein-Tyrosine Phosphatase Promotes FcεRI-Induced Activation of Fyn and Erk Pathways Leading to TNFα Release from Bone Marrow-Derived Mast Cells

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