| First Author | Chambers JE | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 25774599 | Mgi Jnum | J:336380 |
| Mgi Id | MGI:6206040 | Doi | 10.7554/eLife.04872 |
| Citation | Chambers JE, et al. (2015) Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2alpha dephosphorylation. Elife 4 |
| abstractText | Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) to activate the integrated stress response (ISR). In animals, the ISR is antagonised by selective eIF2alpha phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in complex with a PPP1R15-type regulatory subunit. An unbiased search for additional conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin. Like PP1, G-actin associated with the functional core of PPP1R15 family members and G-actin depletion, by the marine toxin jasplakinolide, destabilised the endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin complex was responsive to global changes in the polymeric status of actin, as was its eIF2alpha-directed phosphatase activity, while localised G-actin depletion at sites enriched for PPP1R15 enhanced eIF2alpha phosphorylation and the downstream ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR. |
