TY - JOUR TI - Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration AU - Moehlman, Andrew T AU - Casey, Amanda K AU - Servage, Kelly AU - Orth, Kim AU - Krämer, Helmut A2 - Burd, Christopher G A2 - VijayRaghavan, K VL - 7 PY - 2018 DA - 2018/07/17 SP - e38752 C1 - eLife 2018;7:e38752 DO - 10.7554/eLife.38752 UR - https://doi.org/10.7554/eLife.38752 AB - In response to environmental, developmental, and pathological stressors, cells engage homeostatic pathways to maintain their function. Among these pathways, the Unfolded Protein Response protects cells from the accumulation of misfolded proteins in the ER. Depending on ER stress levels, the ER-resident Fic protein catalyzes AMPylation or de-AMPylation of BiP, the major ER chaperone and regulator of the Unfolded Protein Response. This work elucidates the importance of the reversible AMPylation of BiP in maintaining the Drosophila visual system in response to stress. After 72 hr of constant light, photoreceptors of fic-null and AMPylation-resistant BiPT366A mutants, but not wild-type flies, display loss of synaptic function, disintegration of rhabdomeres, and excessive activation of ER stress reporters. Strikingly, this phenotype is reversible: photoreceptors regain their structure and function within 72 hr once returned to a standard light:dark cycle. These findings show that Fic-mediated AMPylation of BiP is required for neurons to adapt to transient stress demands. KW - unfolded protein response KW - fic domain KW - rhabdomeres KW - ER stress KW - visual system JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -