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PMID: 10330444 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Synaptotagmin II negatively regulates Ca2+-triggered exocytosis of lysosomes in mast cells.

The Journal of experimental medicine ·Vol. 189 ·No. 10 ·1999-05-17 ·Pages 1649-58

Baram D, Adachi R, Medalia O, Tuvim M, Dickey BF, Mekori YA, Sagi-Eisenberg R

Abstract

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 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.

MeSH Terms
Animals Calcimycin Calcium/metabolism Cathepsin D/metabolism Cytoplasmic Granules/immunology Exocytosis/immunology Gene Expression Regulation Lysosomes/immunology,metabolism Mast Cells/metabolism Mice Mice, Inbred BALB C Nerve Tissue Proteins/genetics,metabolism RNA, Messenger/metabolism Rats Rats, Wistar Receptors, IgE/metabolism Serotonin/metabolism Synaptotagmin II Tetradecanoylphorbol Acetate Transfection beta-N-Acetylhexosaminidases/metabolism
Chemicals
Nerve Tissue Proteins RNA, Messenger Receptors, IgE Synaptotagmin II Syt2 protein, mouse Syt2 protein, rat Serotonin Calcimycin beta-N-Acetylhexosaminidases Cathepsin D Tetradecanoylphorbol Acetate Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Baram D
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Adachi R
Medalia O
Tuvim M
Dickey B F
Mekori Y A
Sagi-Eisenberg R
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.189.10.1649
Published
1999-05-17
Pages
1649-58
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193646
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.189.10.1649 PMC Full Text View journal details
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