Substrate specificity of Pasteurella multocida toxin for α subunits of heterotrimeric G proteins.

Pasteurella multocida is the causative agent of a number of epizootic and zoonotic diseases. Its major virulence factor associated with atrophic rhinitis in animals and dermonecrosis in bite wounds is P. multocida toxin (PMT).

Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation.

Pasteurella multocida toxin is a major virulence factor of Pasteurella multocida, which causes pasteurellosis in men and animals and atrophic rhinitis in rabbits and pigs. The approximately 145 kDa protein toxin stimulates various signal transduction pathways by activating heterotrimeric G proteins of the Galpha(q), Galpha(i), and Galpha(12/13) families by using an as yet unknown mechanism. Here, we show that Pasteurella multocida toxin deamidates glutamine-205 of Galpha(i2) to glutamic acid.

Activation of Galpha (i) and subsequent uncoupling of receptor-Galpha(i) signaling by Pasteurella multocida toxin.

Bacterial protein toxins are powerful tools for elucidating signaling mechanisms in eukaryotic cells. A number of bacterial protein toxins, e.g.

The cation-independent mannose 6-phosphate receptor is involved in lysosomal delivery of serglycin.

To clarify the sorting mechanism of the lysosomal/granular proteoglycan serglycin, we treated human promonocytic U937 cells with p-nitrophenyl-beta-D-xyloside (PNP-xyl) and cycloheximide. In the absence of protein synthesis, the carbohydrate moiety of serglycin was synthesized as PNP-xyl-chondroitin sulfate (CS), and most of it was delivered to lysosomes and degraded. Further, an augmented lysosomal targeting of serglycin in the presence of tunicamycin suggested that a sorting/lectin receptor with multiple specificity was involved with an increased capacity for serglycin in the absence of N-glycosylation.