Showing papers by "Ronit Sagi-Eisenberg published in 2001"

Synaptotagmin regulates mast cell functions.

Abstract: Synaptotagmin(s) (Syts), are products of a gene family implicated in the control of Ca2+-dependent exocytosis. Mast cells, specialized secretory cells that release mediators of inflammatory and allergic reactions in a process of regulated exocytosis, express Syt homologues and SNAREs (Soluble NSF Attachment proteins Receptors), which together with Syt constitute the core complex which mediates exocytotic vesicle docking and fusion. Rat basophilic leukemia cells (RBL-2H3), a tumor analogue of mucosal mast cells, express the Syt homologues Syt II, Syt III and Syt V Expression of Syt I, the neuronal Ca2+ sensor, in the RBL cells, resulted in its targeting to secretory granules and in prominent potentiation and acceleration of Ca2+-dependent exocytosis. Syt II is localized to an amine-free lysosomal compartment, which is also subjected to regulated exocytosis. Lysosomal exocytosis is negatively regulated by Syt II: overexpression of Syt II inhibited Ca2+-triggered exocytosis of lysosomes, while suppression of Syt II expression markedly potentiated this release. These findings implicate Syt homologues as key regulators of mast cell function.

Gi-Mediated Activation of the Syk Kinase by the Receptor Mimetic Basic Secretagogues of Mast Cells: Role in Mediating Arachidonic Acid/Metabolites Release

Abstract: Syk kinase is essential for FceRI-mediated signaling and release of inflammatory mediators from mast cells We now show that activation of rat peritoneal mast cells by the nonimmunological, G i -mediated pathway also results in the activation of Syk We show that compound 48/80 (c48/80), a receptor analogue that activates directly G proteins, activates Syk in a pertussis toxin-sensitive fashion We further show that Syk activation by c48/80 is blocked by the protein kinase C inhibitor GF109203X, by the phosphatidylinositol 3-kinase inhibitors, wortmannin and LY294002, by EGTA, and by the selective src -like kinase inhibitor PP1 These results suggest that in the nonimmunological, G i -mediated pathway, Syk is located downstream from phospholipase C and phosphatidylinositol 3-kinase However, in common with the FceRI-mediated pathway, activation of Syk by c48/80 is dependent on a src -like protein tyrosine kinase Finally, we show that in the nonimmunological pathway, Syk plays a central role in the release of arachidonic acid/eicosanoid metabolites, but not in the release of prestored mediators such as histamine

Synaptotagmin regulates mast cell functions

Abstract: Synaptotagmin(s) (Syts), are products of a gene family implicated in the control of Ca2+-dependent exocytosis. Mast cells, specialized secretory cells that release mediators of inflammatory and allergic reactions in a process of regulated exocytosis, express Syt homologues and SNAREs (Soluble NSF Attachment proteins Receptors), which together with Syt constitute the core complex which mediates exocytotic vesicle docking and fusion. Rat basophilic leukemia cells (RBL-2H3), a tumor analogue of mucosal mast cells, express the Syt homologues Syt II, Syt III and Syt V Expression of Syt I, the neuronal Ca2+ sensor, in the RBL cells, resulted in its targeting to secretory granules and in prominent potentiation and acceleration of Ca2+-dependent exocytosis. Syt II is localized to an amine-free lysosomal compartment, which is also subjected to regulated exocytosis. Lysosomal exocytosis is negatively regulated by Syt II: overexpression of Syt II inhibited Ca2+-triggered exocytosis of lysosomes, while suppression of Syt II expression markedly potentiated this release. These findings implicate Syt homologues as key regulators of mast cell function.