title: 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.
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. nclemons@illinois.edu.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Clemons
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. sluo815@gmail.com.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. mengho@life.illinois.edu.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Ho
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. bawilson@life.illinois.edu.
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Wilson
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology* / Q000473:pathology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D021381:Protein Transport; D013379:Substrate Specificity; D014162:Transfection; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C062258:Pasteurella multocida toxin; D037521:Virulence Factors; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: G-protein downregulation; Pasteurella multocida; deamidation; dermonecrosis; mitogen