[PDF][PDF] GRASP55 and UPR control interleukin-1β aggregation and secretion
M Chiritoiu, N Brouwers, G Turacchio, M Pirozzi… - Developmental cell, 2019 - cell.com
Developmental cell, 2019•cell.com
Signal-sequence-lacking interleukin (IL)-1β, is cleaved by caspase-1 to mature mIL-1β,
which is secreted, without entering the endoplasmic reticulum. We report that macrophages
of GRASP55−/− mice are defective in mIL-1β secretion and retain it as intracellular
aggregates. Intriguingly, GRASP55−/− macrophages are defective in the IRE1α branch of
the unfolded protein response. This finding fits well with our data that inhibition of IRE1α also
impairs mIL-1β secretion and causes its accumulation in intracellular aggregates. PERK …
which is secreted, without entering the endoplasmic reticulum. We report that macrophages
of GRASP55−/− mice are defective in mIL-1β secretion and retain it as intracellular
aggregates. Intriguingly, GRASP55−/− macrophages are defective in the IRE1α branch of
the unfolded protein response. This finding fits well with our data that inhibition of IRE1α also
impairs mIL-1β secretion and causes its accumulation in intracellular aggregates. PERK …
Summary
Signal-sequence-lacking interleukin (IL)-1β, is cleaved by caspase-1 to mature mIL-1β, which is secreted, without entering the endoplasmic reticulum. We report that macrophages of GRASP55−/− mice are defective in mIL-1β secretion and retain it as intracellular aggregates. Intriguingly, GRASP55−/− macrophages are defective in the IRE1α branch of the unfolded protein response. This finding fits well with our data that inhibition of IRE1α also impairs mIL-1β secretion and causes its accumulation in intracellular aggregates. PERK inhibition, on the other hand, controls caspase-1-mediated conversion of proIL-1β to mIL-1β. These findings reveal translation-independent functions of PERK and IRE1α: PERK controls the production of mIL-1β, which is then followed by GRASP55 and IRE1α activity to keep mIL-1β in a secretion-competent form.
cell.com