Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration
- University of Texas Southwestern Medical Center, United States
Abstract
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 hours 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 hours 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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute of General Medical Sciences (R01GM120196)
- Helmut Krämer
National Eye Institute (RO1EY010199)
- Helmut Krämer
Howard Hughes Medical Institute
- Kim Orth
Welch Foundation (I-1561)
- Kim Orth
Once Upon A Time Foundation
- Kim Orth
National Science Foundation (1000176311)
- Andrew T Moehlman
National Institute of General Medical Sciences (RO1GM115188)
- Kim Orth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Moehlman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration
eLife 7:e38752.
https://doi.org/10.7554/eLife.38752
