Synaptotagmin II Negatively Regulates Ca 2 1 - triggered Exocytosis of Lysosomes in Mast Cells
نویسندگان
چکیده
Synaptotagmins (Syts) I and II are believed to act as Ca 2 1 sensors in the control of neurotransmission. Here we demonstrate that mast cells express Syt II in their lysosomal fraction. We further show that activation of mast cells by either aggregation of Fc e RI or by Ca 2 1 ionophores results in exocytosis of lysosomes, in addition to the well documented exocytosis of their secretory granules. Syt II directly regulates lysosomal exocytosis, whereby overexpression of Syt II inhibited Ca 2 1 -triggered release of the lysosomal processed form of cathepsin D, whereas suppression of Syt II expression markedly potentiated this release. These findings provide evidence for a novel function of Syt II in negatively regulating Ca 2 1 -triggered exocytosis of lysosomes, and suggest that Syt II–regulated secretion from lysosomes may play an important role in mast cell biology.
منابع مشابه
Synaptotagmin II Negatively Regulates Ca2+-triggered Exocytosis of Lysosomes in Mast Cells
Synaptotagmins (Syts) I and II are believed to act as Ca2+ sensors in the control of neurotransmission. Here we demonstrate that mast cells express Syt II in their lysosomal fraction. We further show that activation of mast cells by either aggregation of FcepsilonRI or by Ca2+ ionophores results in exocytosis of lysosomes, in addition to the well documented exocytosis of their secretory granule...
متن کاملThe Exocytosis-Regulatory Protein Synaptotagmin VII Mediates Cell Invasion by Trypanosoma cruzi
The intracellular protozoan parasite Trypanosoma cruzi causes Chagas' disease, which affects millions of people in Latin America. T. cruzi enters a large number of cell types by an unusual mechanism that involves Ca(2+)-triggered fusion of lysosomes with the plasma membrane. Here we show that synaptotagmin VII (Syt VII), a ubiquitously expressed synaptotagmin isoform that regulates exocytosis o...
متن کاملSynaptotagmin-1 and -7 are functionally overlapping Ca2+ sensors for exocytosis in adrenal chromaffin cells.
Synaptotagmin-1, the canonical isoform of the synaptotagmin family, is a Ca(2+) sensor for fast synchronous neurotransmitter release in forebrain neurons and chromaffin cells. Even though deletion of synaptotagmin-1 abolishes fast exocytosis in chromaffin cells, it reduces overall secretion by only 20% because of the persistence of slow exocytosis. Therefore, another Ca(2+) sensor dominates rel...
متن کاملCell biology of Ca2+-triggered exocytosis.
Ca(2+) triggers many forms of exocytosis in different types of eukaryotic cells, for example synaptic vesicle exocytosis in neurons, granule exocytosis in mast cells, and hormone exocytosis in endocrine cells. Work over the past two decades has shown that synaptotagmins function as the primary Ca(2+)-sensors for most of these forms of exocytosis, and that synaptotagmins act via Ca(2+)-dependent...
متن کاملSynaptotagmin VII as a Plasma Membrane Ca2+ Sensor in Exocytosis
Synaptotagmins I and II are Ca(2+) binding proteins of synaptic vesicles essential for fast Ca(2+)-triggered neurotransmitter release. However, central synapses and neuroendocrine cells lacking these synaptotagmins still exhibit Ca(2+)-evoked exocytosis. We now propose that synaptotagmin VII functions as a plasma membrane Ca(2+) sensor in synaptic exocytosis complementary to vesicular synaptota...
متن کامل