Pasteurella multocida toxin: Targeting mast cell secretory granules during kiss-and-run secretion

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 -