Synaptotagmin I Expression in Mast Cells of Normal Human Tissues, Systemic Mast Cell Disease, and a Human Mast Cell Leukemia Cell Line

Abstract

Synaptotagmin I (STG I) is a Ca(2+) sensor and one of the synaptic vesicle proteins that mediate exocytosis. To determine the mechanism of release of large granules from mast cells, we studied by immunohistochemistry the presence of STG I in mast cells in normal human tissues simultaneously with the mast cell markers mast cell tryptase (tryptase) and c-kit. The tumor cells of systemic mast cell disease (SMCD) and a human mast cell leukemia cell line (HMC-1) were also examined. Human mast cells in normal tissues and the tumor cells of SMCD expressed STG I as well as mast cell tryptase (tryptase) and c-kit. STG I mRNA and its products in HMC-1 were examined by RT-PCR analysis and immunocytochemistry, respectively. STG I expression in HMC-1 cells was compared with that in cells stimulated and non-stimulated by phorbol 12-myristate 13-acetate and also with that in NB-1 and PC12 cells, known to express STG I. STG I mRNA was detected in both non-stimulated and stimulated HMC-1 cells and in NB-1 and PC12 cells. STG I immunoreactivity was weaker than NB-1 or PC12 immunoreactivity. However, it increased in the stimulated HMC-1 cells. Mast cells expressed STG I in various states. STG I may mediate exocytosis of large granules in mast cells.

c-Fos as a Regulator of Degranulation and Cytokine Production in FcεRI-Activated Mast Cells

“…The expression of SYT I increases in stimulated human mast cells as was demonstrated by immunohistochemistry (29). In this study, we observed that the expression of SYT I was elevated in resting SMC (Fig.…”

“…Another protein known to play an important role in the exocytosis of mast cells is SYT I (28,29), which acts as one of the Ca 2ϩ sensors in the synaptic vesicle and mediates exocytosis (42). The expression of SYT I increases in stimulated human mast cells as was demonstrated by immunohistochemistry (29).…”

“…The mRNA levels of SWAP-70 (25,26), VAMP-7 (27), SYT I (28,29), and SYT II (30,31) were determined by real-time PCR. The mRNA levels of SWAP-70, VAMP-7, and SYT I from resting SMC were analyzed, and their levels are significantly lower in c-Fos-deficient SMC compared with the wild-type SMC (Fig.…”

JunB Is Required for IgE-Mediated Degranulation and Cytokine Release of Mast Cells

“…FcR stimulation initiates signaling cascades including the phospholipase C␥1, PI3K and MAPK pathways (7) with subsequent calcium raise in the cytosol (8,9). The increase in intracellular calcium levels, sensed synaptotagmins (SYT) 4 (10,11), is a prerequisite for degranulation mediated by SNARE (soluble NSF attachment receptor) complex formation, which is crucially involved in the fusion of vesicle and plasma membrane. SNARE complexes are composed of small membrane-bound proteins, such as VAMPs (vehicle-associated membrane proteins), SNAPs (synaptosome-associated proteins), and STX (syntaxins) (7,12,13).…”

Structural and functional studies on SNAREs-mediated membrane fusion

“…Previous studies suggested that synaptotagmin 1 is expressed in mast cells and regulates mast cell function (Baram et al, 1999;Baram et al, 1998;Kimura et al, 2001). The role of…”