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

Abstract
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.
AuthorsNathan C Clemons, Shuhong Luo, Mengfei Ho, Brenda A Wilson
JournalToxins (Toxins (Basel)) Vol. 8 Issue 8 (08 01 2016) ISSN: 2072-6651 [Electronic] Switzerland
PMID27490568 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Proteins
  • Bacterial Toxins
  • Pasteurella multocida toxin
  • Virulence Factors
  • GTP-Binding Protein alpha Subunits, Gq-G11
Topics
  • Bacterial Proteins (genetics, metabolism)
  • Bacterial Toxins (genetics, metabolism)
  • Catalysis
  • Cell Membrane (enzymology, pathology)
  • GTP-Binding Protein alpha Subunits, Gq-G11 (genetics, metabolism)
  • HEK293 Cells
  • Humans
  • Mutation
  • Protein Transport
  • Substrate Specificity
  • Transfection
  • Virulence Factors (genetics, metabolism)

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