| First Author | Chiritoiu M | Year | 2019 |
| Journal | Dev Cell | Volume | 49 |
| Issue | 1 | Pages | 145-155.e4 |
| PubMed ID | 30880003 | Mgi Jnum | J:274869 |
| Mgi Id | MGI:6296685 | Doi | 10.1016/j.devcel.2019.02.011 |
| Citation | Chiritoiu M, et al. (2019) GRASP55 and UPR Control Interleukin-1beta Aggregation and Secretion. Dev Cell 49(1):145-155.e4 |
| abstractText | Signal-sequence-lacking interleukin (IL)-1beta, is cleaved by caspase-1 to mature mIL-1beta, which is secreted, without entering the endoplasmic reticulum. We report that macrophages of GRASP55(-/-) mice are defective in mIL-1beta secretion and retain it as intracellular aggregates. Intriguingly, GRASP55(-/-) macrophages are defective in the IRE1alpha branch of the unfolded protein response. This finding fits well with our data that inhibition of IRE1alpha also impairs mIL-1beta secretion and causes its accumulation in intracellular aggregates. PERK inhibition, on the other hand, controls caspase-1-mediated conversion of proIL-1beta to mIL-1beta. These findings reveal translation-independent functions of PERK and IRE1alpha: PERK controls the production of mIL-1beta, which is then followed by GRASP55 and IRE1alpha activity to keep mIL-1beta in a secretion-competent form. |
