Involvement of filamentous actin in setting the threshold for degranulation in mast cells.
Previous studies using cytochalasins and latrunculin B, inhibitors of actin polymerization, showed that filamentous (F)-actin had a negative regulatory role in Fc epsilon receptor I (Fc epsilon RI) signaling. How F-actin is involved in regulating the activation of mast cells is unknown. In this study we investigated the role of F-actin in mast cell activation induced by aggregation of the glycosylphosphatidylinositol (GPI)-anchored proteins Thy-1 and TEC-21, and compared it to activation via Fc epsilon RI. Pretreatment of rat basophilic leukemia cells with latrunculin B inhibited the Thy-1-induced actin polymerization and elevated the Thy-1-mediated secretory and calcium responses. Inhibition of actin polymerization followed by Thy-1 aggregation resulted in an increased tyrosine phosphorylation of Syk, phospholipase C gamma (PLC gamma), Gab2 and linker for activation of T cells (LAT) adapters, and some other signaling molecules. Enzymatic activities of phosphatidylinositol 3-kinase, PLC gamma, and phosphatase SHP-2 were also up-regulated, but tyrosine phosphorylation of ezrin was inhibited. Similar changes were observed in Fc epsilon RI-activated cells. Significant changes in intracellular distribution, tyrosine phosphorylation, and/or enzymatic activities of signaling molecules occurred in latrunculin-pretreated cells before cell triggering. The combined data suggest that actin polymerization is critical for setting the thresholds for mast cell signaling via aggregation of both Fc epsilon RI and GPI-anchored proteins.
Tolarová
Helena
H
Department of Signal Transduction, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Dráberová
Lubica
L
Heneberg
Petr
P
Dráber
Petr
P
D000199:Actins / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology / Q000502:physiology*; D045744:Cell Line, Tumor; D004792:Enzyme Precursors / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D051381:Rats; D011940:Receptor Aggregation / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D018800:Thy-1 Antigens / Q000276:immunology; D010738:Type C Phospholipases / Q000276:immunology
D000199:Actins; D000954:Antigens, Surface; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D017455:Receptors, IgE; D000072377:Syk Kinase; D013844:Thiazoles; D053778:Thiazolidines; D018800:Thy-1 Antigens; D010738:Type C Phospholipases; C450042:TEX101 protein, rat; C000606898:Syk protein, rat; C037068:latrunculin B