作者
Hongwei Ma, Michael R Butler, Arjun Thapa, Josh Belcher, Fan Yang, Wolfgang Baehr, Martin Biel, Stylianos Michalakis, Xi-Qin Ding
发表日期
2015/8/21
期刊
Journal of Biological Chemistry
卷号
290
期号
34
页码范围
20880-20892
出版商
Elsevier
简介
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 Ca2+ 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 …
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H Ma, MR Butler, A Thapa, J Belcher, F Yang, W Baehr… - Journal of Biological Chemistry, 2015