| First Author | Cho H | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 22 | Pages | 4561-71 |
| PubMed ID | 22966200 | Mgi Jnum | J:189238 |
| Mgi Id | MGI:5444787 | Doi | 10.1128/MCB.00651-12 |
| Citation | Cho H, et al. (2012) The Loss of RGS Protein-Galphai2 Interactions Results in Markedly Impaired Mouse Neutrophil Trafficking to Inflammatory Sites. Mol Cell Biol 32(22):4561-71 |
| abstractText | Neutrophils are first responders rapidly mobilized to inflammatory sites by a tightly regulated, nonredundant hierarchy of chemoattractants. These chemoattractants engage neutrophil cell surface receptors triggering heterotrimeric G-protein Galpha(i) subunits to exchange GDP for GTP. By limiting the duration that Galpha(i) subunits remain GTP bound, RGS proteins modulate chemoattractant receptor signaling. Here, we show that neutrophils with a genomic knock in of a mutation that disables regulator of G-protein signaling (RGS)-Galpha(i2) interactions accumulate in the bone marrow and mobilize poorly to inflammatory sites. These defects are attributable to enhanced sensitivity to background signals, prolonged chemoattractant receptor signaling, and inappropriate CXCR2 downregulation. Intravital imaging revealed a failure of the mutant neutrophils to accumulate at and stabilize sites of sterile inflammation. Furthermore, these mice could not control a nonlethal Staphylococcus aureus infection. Neutrophil RGS proteins establish a threshold for Galpha(i) activation, helping to coordinate desensitization mechanisms. Their loss renders neutrophils functionally incompetent. |
