Adaptation to Constant Light Requires Fic-mediated AMPylation of BiP to Protect Against Reversible Photoreceptor Degeneration

Overview

Journal Elife

Specialty Biology

Date 2018 Jul 18

PMID 30015618

Citations 17

Authors

Andrew T Moehlman

Amanda K Casey

Kelly Servage

Kim Orth

Helmut Kramer

Affiliations

Soon will be listed here.

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 visual system in response to stress. After 72 hr of constant light, photoreceptors of -null and AMPylation-resistant 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.

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References

Webel R, Menon I, OTousa J, Colley N . Role of asparagine-linked oligosaccharides in rhodopsin maturation and association with its molecular chaperone, NinaA. J Biol Chem. 2000; 275(32):24752-9. DOI: 10.1074/jbc.M002668200. View

Bertolotti A, Zhang Y, Hendershot L, Harding H, Ron D . Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2000; 2(6):326-32. DOI: 10.1038/35014014. View

Kiselev A, Socolich M, Vinos J, Hardy R, Zuker C, Ranganathan R . A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila. Neuron. 2000; 28(1):139-52. DOI: 10.1016/s0896-6273(00)00092-1. View

Lee S, Montell C . Regulation of the rhodopsin protein phosphatase, RDGC, through interaction with calmodulin. Neuron. 2002; 32(6):1097-106. DOI: 10.1016/s0896-6273(01)00538-4. View

Kalidas S, Smith D . Novel genomic cDNA hybrids produce effective RNA interference in adult Drosophila. Neuron. 2002; 33(2):177-84. DOI: 10.1016/s0896-6273(02)00560-3. View

Johnson K, Grawe F, Grzeschik N, Knust E . Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration. Curr Biol. 2002; 12(19):1675-80. DOI: 10.1016/s0960-9822(02)01180-6. View

Meunier L, Usherwood Y, Chung K, Hendershot L . A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell. 2002; 13(12):4456-69. PMC: 138646. DOI: 10.1091/mbc.e02-05-0311. View

Borycz J, Borycz J, Loubani M, Meinertzhagen I . tan and ebony genes regulate a novel pathway for transmitter metabolism at fly photoreceptor terminals. J Neurosci. 2002; 22(24):10549-57. PMC: 6758454. View

Ma Y, Hendershot L . Delineation of a negative feedback regulatory loop that controls protein translation during endoplasmic reticulum stress. J Biol Chem. 2003; 278(37):34864-73. DOI: 10.1074/jbc.M301107200. View

10.

Lee S, Xu H, Kang L, Amzel L, Montell C . Light adaptation through phosphoinositide-regulated translocation of Drosophila visual arrestin. Neuron. 2003; 39(1):121-32. DOI: 10.1016/s0896-6273(03)00390-8. View

11.

Leonard D, Bowman V, Ready D, Pak W . Degeneration of photoreceptors in rhodopsin mutants of Drosophila. J Neurobiol. 1992; 23(6):605-26. DOI: 10.1002/neu.480230602. View

12.

Lee S, Montell C . Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway. Curr Biol. 2004; 14(23):2076-85. DOI: 10.1016/j.cub.2004.11.054. View

13.

Shen J, Snapp E, Lippincott-Schwartz J, Prywes R . Stable binding of ATF6 to BiP in the endoplasmic reticulum stress response. Mol Cell Biol. 2005; 25(3):921-32. PMC: 543992. DOI: 10.1128/MCB.25.3.921-932.2005. View

14.

Rosenbaum E, Hardie R, Colley N . Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival. Neuron. 2006; 49(2):229-41. PMC: 3414428. DOI: 10.1016/j.neuron.2005.12.011. View

15.

Hegde N, Chevalier M, Wisner T, Denton M, Shire K, Frappier L . The role of BiP in endoplasmic reticulum-associated degradation of major histocompatibility complex class I heavy chain induced by cytomegalovirus proteins. J Biol Chem. 2006; 281(30):20910-20919. DOI: 10.1074/jbc.M602989200. View

16.

Venken K, He Y, Hoskins R, Bellen H . P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science. 2006; 314(5806):1747-51. DOI: 10.1126/science.1134426. View

17.

Ryoo H, Domingos P, Kang M, Steller H . Unfolded protein response in a Drosophila model for retinal degeneration. EMBO J. 2006; 26(1):242-52. PMC: 1782370. DOI: 10.1038/sj.emboj.7601477. View

18.

Dietzl G, Chen D, Schnorrer F, Su K, Barinova Y, Fellner M . A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature. 2007; 448(7150):151-6. DOI: 10.1038/nature05954. View

19.

Tran E, Zhou Y, Corbett A, Wente S . The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein remodeling events. Mol Cell. 2007; 28(5):850-9. DOI: 10.1016/j.molcel.2007.09.019. View

20.

Akbar M, Ray S, Kramer H . The SM protein Car/Vps33A regulates SNARE-mediated trafficking to lysosomes and lysosome-related organelles. Mol Biol Cell. 2009; 20(6):1705-14. PMC: 2655250. DOI: 10.1091/mbc.e08-03-0282. View