Synaptotagmin regulates mast cell functions

Synaptotagmin(s) (Syts), are products of a gene family implicated in the co ntrol 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 At tachment proteins Receptors), which together with Syt constitute the core c omplex 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 neur onal Ca2+ sensor, in the RBL cells, resulted in its targeting to secretory granules and in prominent potentiation and acceleration of Ca2+-dependent e xocytosis. Syt II is localized to an amine-free lysosomal compartment, whic h is also subjected to regulated exocytosis. Lysosomal exocytosis is negati vely regulated by Syt II: overexpression of Syt II inhibited Ca2+-triggered exocytosis of lysosomes, while suppression of Syt II expression markedly p otentiated this release. These findings implicate Syt homologues as key reg ulators of mast cell function.