NDLI: cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

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cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

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cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Biel, Martin Yang, Fan Baehr, Wolfgang Michalakis, Stylianos Ding, Xi-qin Ma, Hongwei Belcher, Josh Butler, Michael R. Thapa, Arjun
Description	Author Affiliation: Ma H ( From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.); Butler MR ( From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.); Thapa A ( From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.); Belcher J ( From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.); Yang F ( From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.); Baehr W ( the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah 84132, and.); Biel M ( the Center for Integrated Protein Science Munich and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.); Michalakis S ( the Center for Integrated Protein Science Munich and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.); Ding XQ ( From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, xi-qin-ding@ouhsc.edu.)
Abstract	Photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in phototransduction. Mutations in the cone CNG channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. We have shown endoplasmic reticulum (ER) stress-associated apoptotic cone death and increased phosphorylation of the ER Ca(2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in CNG channel-deficient mice. We also presented a remarkable elevation of cGMP and an increased activity of the cGMP-dependent protein kinase (protein kinase G, PKG) in CNG channel deficiency. This work investigated whether cGMP/PKG signaling regulates ER stress and IP3R1 phosphorylation in CNG channel-deficient cones. Treatment with PKG inhibitor and deletion of guanylate cyclase-1 (GC1), the enzyme producing cGMP in cones, were used to suppress cGMP/PKG signaling in cone-dominant Cnga3(-/-)/Nrl(-/-) mice. We found that treatment with PKG inhibitor or deletion of GC1 effectively reduced apoptotic cone death, increased expression levels of cone proteins, and decreased activation of Müller glial cells. Furthermore, we observed significantly increased phosphorylation of IP3R1 and reduced ER stress. Our findings demonstrate a role of cGMP/PKG signaling in ER stress and ER Ca(2+) channel regulation and provide insights into the mechanism of cone degeneration in CNG channel deficiency.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	34
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-08-21
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cyclic GMP-Dependent Protein Kinases Metabolism Cyclic GMP Cyclic Nucleotide-Gated Cation Channels Genetics Endoplasmic Reticulum Stress Inositol 1,4,5-Trisphosphate Receptors Retinal Cone Photoreceptor Cells Animals Apoptosis Basic-Leucine Zipper Transcription Factors Deficiency Carbazoles Pharmacology Analogs & Derivatives Antagonists & Inhibitors Ependymoglial Cells Cytology Eye Proteins Gene Expression Regulation Guanylate Cyclase Mice Mice, Knockout Phosphorylation Protein Kinase Inhibitors Receptors, Cell Surface Signal Transduction Thionucleotides Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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