Pasteurella multocida toxin: Targeting mast cell secretory granules during kiss-and-run secretion. Issue 1 (February 2016)

• Record Type: Journal Article
• Authors: Danielsen, Elisabeth M.; Christiansen, Nina; Danielsen, E. Michael
• Is Part Of: Tissue & cell. Volume 48:Issue 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-02
• Subjects: PMT Pasteurella multocida toxin -- CTB V. cholera toxin B-subunit -- SDS/PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis; Pasteurella multocida toxin (PMT) -- V. cholera toxin B-subunit (CTB) -- Small intestine -- Mast cells -- Secretory granules -- Kiss-and-run; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2015.12.005
• Languages: English
• ISSNs: 0040-8166

Abstract

Graphical abstract: Highlights: Pasteurella multocida toxin (PMT) accumulates in granules of mucosal mast cells. PMT entry into granules is insensitive to low temperature. PMT may enter mast cell granules during their kiss-and-run cycle of exocytosis. Abstract: 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.