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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2017 ; 292
(9
): 3909-3918
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Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of
Polyamine from Mast Cells
#MMPMID28082679
Takeuchi T
; Harada Y
; Moriyama S
; Furuta K
; Tanaka S
; Miyaji T
; Omote H
; Moriyama Y
; Hiasa M
J Biol Chem
2017[Mar]; 292
(9
): 3909-3918
PMID28082679
show ga
Mast cells are secretory cells that play an important role in host defense by
discharging various intragranular contents, such as histamine and serotonin, upon
stimulation of Fc receptors. The granules also contain spermine and spermidine,
which can act as modulators of mast cell function, although the mechanism
underlying vesicular storage remains unknown. Vesicular polyamine transporter
(VPAT), the fourth member of the SLC18 transporter family, is an active
transporter responsible for vesicular storage of spermine and spermidine in
neurons. In the present study, we investigated whether VPAT functions in mast
cells. RT-PCR and Western blotting indicated VPAT expression in murine bone
marrow-derived mast cells (BMMCs). Immunohistochemical analysis indicated that
VPAT is colocalized with VAMP3 but not with histamine, serotonin, cathepsin D,
VAMP2, or VAMP7. Membrane vesicles from BMMCs accumulated spermidine upon the
addition of ATP in a reserpine- and bafilomycin A(1)-sensitive manner. BMMCs
secreted spermine and spermidine upon the addition of either antigen or A23187 in
the presence of Ca(2+), and the antigen-mediated release, which was shown to be
temperature-dependent and sensitive to bafilomycin A(1) and tetanus toxin, was
significantly suppressed by VPAT gene RNA interference. Under these conditions,
expression of vesicular monoamine transporter 2 was unaffected, but
antigen-dependent histamine release was significantly suppressed, which was
recovered by the addition of 1 mm spermine. These results strongly suggest that
VPAT is expressed and is responsible for vesicular storage of spermine and
spermidine in novel secretory granules that differ from histamine- and
serotonin-containing granules and is involved in vesicular release of these
polyamines from mast cells.
|Animals
[MESH]
|Calcimycin/chemistry
[MESH]
|Calcium/chemistry
[MESH]
|Cathepsin D/chemistry
[MESH]
|Cation Transport Proteins/*metabolism
[MESH]
|Exocytosis
[MESH]
|Histamine Release
[MESH]
|Histamine/chemistry
[MESH]
|Immunohistochemistry
[MESH]
|Male
[MESH]
|Mast Cells/cytology/*metabolism
[MESH]
|Mice
[MESH]
|Microscopy, Fluorescence
[MESH]
|Polyamines/*metabolism
[MESH]
|R-SNARE Proteins/metabolism
[MESH]
|Rats
[MESH]
|Rats, Wistar
[MESH]
|Secretory Vesicles/metabolism
[MESH]
|Serotonin/chemistry
[MESH]
|Spermidine/metabolism
[MESH]
|Spermine/metabolism
[MESH]
|Vesicle-Associated Membrane Protein 2/metabolism
[MESH]
|Vesicle-Associated Membrane Protein 3/metabolism
[MESH]