Sensory quiescence induces a cell-non-autonomous integrated stress response curbed by condensate formation of the ATF4 and XRP1 effectors.

ABSTRACT: Sensory disabilities have been identified as significant risk factors for dementia but underlying molecular mechanisms are unknown. In different Drosophila models with loss of sensory input, we observe non-autonomous induction of the integrated stress response (ISR) deep in the brain, as indicated by eIF2α^S50 phosphorylation-dependent elevated levels of the ISR effectors ATF4 and XRP1. Unlike during canonical ISR, however, the ATF4 and XRP1 transcription factors are enriched in cytosolic granules that are positive for RNA and the stress granule markers Caprin, FMR1, and p62, and are reversible upon restoration of vision for blind flies. Cytosolic restraint of the ATF4 and XRP1 transcription factors dampens expression of their downstream targets including genes of cell death path

SUBMITTER: Shekhar S 

PROVIDER: S-EPMC11695831 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature