The Journal of Experimental Medicine
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*12-O-TETRADECANOYLPHORBOL-13-ACETATE
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*CALCIUM, ELEMENTAL
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© The Rockefeller University Press, 0022-1007/1999/5/1649/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1649-1658

Articles

Synaptotagmin II Negatively Regulates Ca2+-triggered Exocytosis of Lysosomes in Mast Cells

Dana Baram*,{ddagger}, Roberto Adachi§, Ora Medalia*, Michael Tuvim§, Burton F. Dickey§, Yoseph A. Mekori{ddagger}, and Ronit Sagi-Eisenberg*

From the * Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel; the {ddagger} Allergy and Clinical Immunology Unit, Sapir Medical Center, Kfar Saba, 44281, Israel; and the § Departments of Medicine and Cell Biology, Baylor College of Medicine, Houston, Texas 77030

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 Fc{varepsilon}RI or by Ca2+ 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 Ca2+-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 Ca2+-triggered exocytosis of lysosomes, and suggest that Syt II–regulated secretion from lysosomes may play an important role in mast cell biology.

Key Words: mast cells • lysosomes • calcium binding proteins • exocytosis • immunoglobulin E

Address correspondence to Ronit Sagi-Eisenberg, Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel. Phone: 972-3-640-9500; Fax: 972-3-640-7432; E-mail: histol3.ccsg.tau.ac.il

Abbreviations used: BMMC, bone marrow-derived mast cell; RBL, rat basophilic leukemia; RPMC, rat peritoneal mast cell; SG, secretory granule; SV, synaptic vesicle; Syt, synaptotagmin; TPA, 12-O-tetradecanoylphorbol-13-acetate.


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