TY - JOUR
T1 - Pasteurella multocida toxin
T2 - Targeting mast cell secretory granules during kiss-and-run secretion
AU - Danielsen, Elisabeth Margrethe
AU - Christiansen, Nina
AU - Danielsen, Erik Michael
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Pasteurella multocida toxin (PMT), a virulence factor of the pathogenic Gram-negative bacterium P. multocida, is a 146 kDa protein belonging to the A–B class of toxins. Once inside a target cell, the A domain deamidates the α-subunit of heterotrimeric G-proteins, thereby activating downstream signaling cascades. However, little is known about how PMT selects and enters its cellular targets. We therefore studied PMT binding and uptake in porcine cultured intestinal mucosal explants to identify susceptible cells in the epithelium and underlying lamina propria. In comparison with Vibrio cholera B-subunit, a well-known enterotoxin taken up by receptor-mediated endocytosis, PMT binding to the epithelial brush border was scarce, and no uptake into enterocytes was detected by 2 h, implying that none of the glycolipids in the brush border are a functional receptor for PMT. However, in the lamina propria, PMT distinctly accumulated in the secretory granules of mast cells. This also occurred at 4 °C, ruling out endocytosis, but suggestive of uptake via pores that connect the granules to the cell surface. Mast cell granules are known to secrete their contents by a “kiss-and-run” mechanism, and we propose that PMT may exploit this secretory mechanism to gain entry into this particular cell type.
AB - Pasteurella multocida toxin (PMT), a virulence factor of the pathogenic Gram-negative bacterium P. multocida, is a 146 kDa protein belonging to the A–B class of toxins. Once inside a target cell, the A domain deamidates the α-subunit of heterotrimeric G-proteins, thereby activating downstream signaling cascades. However, little is known about how PMT selects and enters its cellular targets. We therefore studied PMT binding and uptake in porcine cultured intestinal mucosal explants to identify susceptible cells in the epithelium and underlying lamina propria. In comparison with Vibrio cholera B-subunit, a well-known enterotoxin taken up by receptor-mediated endocytosis, PMT binding to the epithelial brush border was scarce, and no uptake into enterocytes was detected by 2 h, implying that none of the glycolipids in the brush border are a functional receptor for PMT. However, in the lamina propria, PMT distinctly accumulated in the secretory granules of mast cells. This also occurred at 4 °C, ruling out endocytosis, but suggestive of uptake via pores that connect the granules to the cell surface. Mast cell granules are known to secrete their contents by a “kiss-and-run” mechanism, and we propose that PMT may exploit this secretory mechanism to gain entry into this particular cell type.
U2 - 10.1016/j.tice.2015.12.005
DO - 10.1016/j.tice.2015.12.005
M3 - Journal article
C2 - 26763205
SN - 0040-8166
VL - 48
SP - 1
EP - 9
JO - Tissue and Cell
JF - Tissue and Cell
IS - 1
ER -
