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 | Nathan C Clemons, Shuhong Luo, Mengfei Ho, Brenda A Wilson |
Journal | Toxins
(Toxins (Basel))
Vol. 8
Issue 8
(08 01 2016)
ISSN: 2072-6651 [Electronic] Switzerland |
PMID | 27490568
(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)
|