Figure 7.

Working model for the impact of cellular stress and ISRIB in eIF2B bodies of astrocytes

(A) eIF2B localizes to small eIF2B bodies containing catalytic subcomplexes and larger eIF2B bodies containing a variety of regulatory subcomplexes (including decameric eIF2B).

(B) Upon the activation of the acute ISR program, eIF2Bγδε subcomplexes are formed and localized to small eIF2B bodies which we hypothesize to have a regulatory role in eIF2B GEF activity; whilst large eIF2B bodies are negatively impacted.

(C) During the transition to a chronic ISR, eIF2Bδ distribution in small bodies is reversed and GEF activity is restored to basal rates, whereas ISRIB treatment bypasses transient eIF2Bδ distribution by prompting extended eIF2Bγδε formation by direct interaction with eIF2Bδ.