Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration

Andrew T. Moehlman, Amanda K. Casey, Kelly Servage, Kim Orth, Helmut Krämer

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.

Original languageEnglish (US)
Article numbere38752
JournaleLife
Volume7
DOIs
StatePublished - Jul 17 2018

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Unfolded Protein Response
Light
Photoperiod
Diptera
Drosophila
Proteins
Phenotype
Neurons
Regain
Disintegration
Chemical activation
Display devices

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration. / Moehlman, Andrew T.; Casey, Amanda K.; Servage, Kelly; Orth, Kim; Krämer, Helmut.

In: eLife, Vol. 7, e38752, 17.07.2018.

Research output: Contribution to journalArticle

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