Pasteurella multocida toxin

Wilson, Brenda A.; Bergmann, Stefan; Ho, Mengfei; Orth, J.

doi:10.1016/b978-0-12-800188-2.00017-3

Cited by 3 publications

(2 citation statements)

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“…PMT is a 1285-amino acid AB protein toxin that acts intracellularly by gaining entry into host cells via binding membrane phospholipids phosphatidylcholine, sphingomyelin, and an as-yet unknown trypsin-sensitive protein partner [ 2 ]. PMT is subsequently endocytosed and released from the late endosomes into the cytosol in a pH dependent manner [ 3 , 4 , 5 ], where it targets heterotrimeric G-proteins and modulates their downstream signaling pathways (reviewed in [ 6 ]). PMT acts on α subunits of the Gα q/11 , Gα 12/13 , and Gα i 1/2/3 , but not Gα s families [ 7 , 8 , 9 , 10 ] through deamidation of a specific Gln residue in the switch II region of the active site of Gα subunits [ 11 ], changing Glu to Gln and converting the Gα-protein into a constitutively active form.…”

Section: Introductionmentioning

confidence: 99%

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Selective Membrane Redistribution and Depletion of Gαq-Protein by Pasteurella multocida Toxin

Clemons

Luo

et al. 2016

Toxins

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Pasteurella multocida toxin (PMT), the major virulence factor responsible for zoonotic atrophic rhinitis, is a protein deamidase that activates the alpha subunit of heterotrimeric G proteins. Initial activation of G alpha-q-coupled phospholipase C-beta-1 signaling by PMT is followed by uncoupling of G alpha-q-dependent signaling, causing downregulation of downstream calcium and mitogenic signaling pathways. Here, we show that PMT decreases endogenous and exogenously expressed G alpha-q protein content in host cell plasma membranes and in detergent resistant membrane (DRM) fractions. This membrane depletion of G alpha-q protein was dependent upon the catalytic activity of PMT. Results indicate that PMT-modified G alpha-q redistributes within the host cell membrane from the DRM fraction into the soluble membrane and cytosolic fractions. In contrast, PMT had no affect on G alpha-s or G beta protein levels, which are not substrate targets of PMT. PMT also had no affect on G alpha-11 levels, even though G alpha-11 can serve as a substrate for deamidation by PMT, suggesting that membrane depletion of PMT-modified G-alpha-q has specificity.

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Section: Introductionmentioning

confidence: 99%

“…Instead, PMT inhibits adenylate cyclase activity through its activation of inhibitory AC regulators of the Gα i family [ 23 ]. PMT activation of these different G-protein signaling pathways, in conjunction with crosstalk among the downstream signaling pathways, can lead to multiple cellular outcomes (reviewed in [ 6 , 24 ]).…”

Section: Introductionmentioning

confidence: 99%

Selective Membrane Redistribution and Depletion of Gαq-Protein by Pasteurella multocida Toxin

Clemons

Luo

et al. 2016

Toxins

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Biomonitoring of Water and Waste Water

Agrawal

Gopal

2013

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Rho/ROCK-dependent inhibition of 3T3-L1 adipogenesis by G-protein-deamidating dermonecrotic toxins: differential regulation of Notch1, Pref1/Dlk1, and β-catenin signaling

Bannai¹,

Aminova²,

Faulkner³

et al. 2012

Front. Cell. Inf. Microbio.

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The dermonecrotic toxins from Pasteurella multocida (PMT), Bordetella (DNT), Escherichia coli (CNF1-3), and Yersinia (CNFY) modulate their G-protein targets through deamidation and/or transglutamination of an active site Gln residue, which results in activation of the G protein and its cognate downstream signaling pathways. Whereas DNT and the CNFs act on small Rho GTPases, PMT acts on the α subunit of heterotrimeric Gq, Gi, and G12/13 proteins. We previously demonstrated that PMT potently blocks adipogenesis and adipocyte differentiation in a calcineurin-independent manner through downregulation of Notch1 and stabilization of β-catenin and Pref1/Dlk1, key proteins in signaling pathways strongly linked to cell fate decisions, including fat and bone development. Here, we report that similar to PMT, DNT, and CNF1 completely block adipogenesis and adipocyte differentiation by preventing upregulation of adipocyte markers, PPARγ and C/EBPα, while stabilizing the expression of Pref1/Dlk1 and β-catenin. We show that the Rho/ROCK inhibitor Y-27632 prevented or reversed these toxin-mediated effects, strongly supporting a role for Rho/ROCK signaling in dermonecrotic toxin-mediated inhibition of adipogenesis and adipocyte differentiation. Toxin treatment was also accompanied by downregulation of Notch1 expression, although this inhibition was independent of Rho/ROCK signaling. We further show that PMT-mediated downregulation of Notch1 expression occurs primarily through G12/13 signaling. Our results reveal new details of the pathways involved in dermonecrotic toxin action on adipocyte differentiation, and the role of Rho/ROCK signaling in mediating toxin effects on Wnt/β-catenin and Notch1 signaling, and in particular the role of Gq and G12/13 in mediating PMT effects on Rho/ROCK and Notch1 signaling.

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Pasteurella multocida toxin

Cited by 3 publications

References 263 publications

Selective Membrane Redistribution and Depletion of Gαq-Protein by Pasteurella multocida Toxin

Selective Membrane Redistribution and Depletion of Gαq-Protein by Pasteurella multocida Toxin

Biomonitoring of Water and Waste Water

Rho/ROCK-dependent inhibition of 3T3-L1 adipogenesis by G-protein-deamidating dermonecrotic toxins: differential regulation of Notch1, Pref1/Dlk1, and β-catenin signaling

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