Xi-Qin Deng, Associate Professor of Cell Biology, and the Joanne I Moore Professor of Pharmacology at University of Oklahoma Health Sciences Center will be delivering a seminar on “cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency” on Wednesday, January 24th at 12:00 Noon in the Moran Eye Center auditorium.
Abstract: Mutations in the CNGA3 and CNGB3 genes that encode the cone cyclic nucleotide-gated (CNG) channel subunits account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. Cone photoreceptors degenerate over time in patients and in mouse models of CNG channel deficiency. Over the last several years, my laboratory has been investigating the cellular mechanisms of cone degeneration using mouse models with CNG channel deficiency. Upon binding of cyclic guanosine monophosphate (cGMP) under dark conditions, CNG channels open and permit the influx of the calcium and sodium ions necessary to maintain the dark current and cellular calcium homeostasis. We have found CNG channel deficient-cones undergo endoplasmic reticulum (ER) stress-associated apoptosis. All three arms of ER stress are activated in CNG channel deficiency. We also showed elevated cGMP/ cGMP-dependent protein kinase (PKG) signaling in CNG channel deficiency and cone protection following cGMP depletion or PKG inhibition. Moreover, we obtained evidence connecting ER calcium channel dysregulation with ER stress and cone death. The current effort aims to determine the cGMP/PKG signaling regulation of ER homeostasis in CNG channel-deficient cones.