scholarly journals Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency

2017 ◽  
Vol 292 (27) ◽  
pp. 11189-11205 ◽  
Author(s):  
Michael R. Butler ◽  
Hongwei Ma ◽  
Fan Yang ◽  
Joshua Belcher ◽  
Yun-Zheng Le ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cyclic Nucleotide ◽  
Channel Activity ◽  
Gated Channel

scholarly journals 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

2015 ◽  
Vol 290 (34) ◽  
pp. 20880-20892 ◽  
Author(s):  
Hongwei Ma ◽  
Michael R. Butler ◽  
Arjun Thapa ◽  
Josh Belcher ◽  
Fan Yang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Er Stress ◽  
Cyclic Nucleotide ◽  
Protein Kinase G ◽  
Cng Channel ◽  
Inositol 1,4,5 Trisphosphate ◽  
Gated Channel ◽  
Trisphosphate Receptor ◽  
Deficient Mice

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 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 Ca2+ channel regulation and provide insights into the mechanism of cone degeneration in CNG channel deficiency.

Expression of a single gene produces both forms of skeletal muscle cyclic nucleotide-gated channels

1997 ◽  
Vol 273 (6) ◽  
pp. E1140-E1148
Author(s):  
Lorraine C. Santy ◽  
Guido Guidotti
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Nucleotide ◽  
Single Gene ◽  
Rabbit Aorta ◽  
Rabbit Skeletal Muscle ◽  
Channel Activity ◽  
Cyclic Nucleotide Gated Channels ◽  
Gated Channel ◽  
Polymerase Chain ◽  
Two Populations

Cyclic nucleotide-gated cation channels in skeletal muscle are responsible for insulin-activated sodium entry into this tissue (J. E. M. McGeoch and G. Guidotti. J. Biol. Chem. 267: 832–841, 1992). These channels have previously been isolated from rabbit skeletal muscle by 8-bromoguanosine 3′,5′-cyclic monophosphate (8-BrcGMP) affinity chromatography, which separates them into two populations differing in nucleotide affinity [L. C. Santy and G. Guidotti. Am. J. Physiol. 271 ( Endocrinol. Metab. 34): E1051-E1060, 1996]. In this study, a polymerase chain reaction approach was used to identify skeletal muscle cyclic nucleotide-gated channel cDNAs. Rabbit skeletal muscle expresses the same cyclic nucleotide-gated channel as rabbit aorta (M. Biel, W. Altenhofen, R. Hullin, J. Ludwig, M. Freichel, V. Flockerzi, N. Dascal, U. B. Kaupp, and F. Hofmann. FEBS Lett. 329: 134–138, 1993). The entire cDNA for this gene was cloned from rabbit skeletal muscle and an antiserum to this protein produced. Expression of this cDNA produces a 63-kDa protein with cyclic nucleotide-gated channel activity. A similarly sized immunoreactive protein is present in sarcolemma. Purification of the expressed channels reveals that this single gene produces both native skeletal muscle channel populations.

scholarly journals Development of a High-Throughput Ca2+ Flux Screening Assay to Monitor Cyclic Nucleotide-Gated Channel Activity and Evaluate Achromatopsia Disease Mutant Channel Function

2019 ◽  
Vol 116 (3) ◽  
pp. 107a-108a
Author(s):  
Jacqueline Tanaka ◽  
Cristy Almonte ◽  
Elizabeth McDuffie ◽  
Laura Jones ◽  
Dennis Colussi ◽  
...  
Keyword(s):  
High Throughput ◽  
Cyclic Nucleotide ◽  
Channel Activity ◽  
Screening Assay ◽  
Mutant Channel ◽  
Channel Function ◽  
Gated Channel

High-Throughput Ca2+ Flux Assay To Monitor Cyclic Nucleotide-Gated Channel Activity and Characterize Achromatopsia Mutant Channel Function

2019 ◽  
Vol 10 (8) ◽  
pp. 3662-3670
Author(s):  
Marlene A. Jacobson ◽  
Laura J. Jones ◽  
Dennis J. Colussi ◽  
Jacqueline C. Tanaka
Keyword(s):  
High Throughput ◽  
Cyclic Nucleotide ◽  
Channel Activity ◽  
Mutant Channel ◽  
Channel Function ◽  
Gated Channel

scholarly journals Endoplasmic Reticulum Stress-associated Cone Photoreceptor Degeneration in Cyclic Nucleotide-gated Channel Deficiency

2012 ◽  
Vol 287 (22) ◽  
pp. 18018-18029 ◽  
Author(s):  
Arjun Thapa ◽  
Lynsie Morris ◽  
Jianhua Xu ◽  
Hongwei Ma ◽  
Stylianos Michalakis ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cyclic Nucleotide ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Gated Channel

Reconstitution and characterization of two forms of cyclic nucleotide-gated channels from skeletal muscle

1996 ◽  
Vol 271 (6) ◽  
pp. E1051-E1060 ◽  
Author(s):  
L. C. Santy ◽  
G. Guidotti
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Nucleotide ◽  
Rod Outer Segments ◽  
Channel Activity ◽  
Cyclic Monophosphate ◽  
Cyclic Nucleotide Gated Channels ◽  
Muscle Plasma Membrane ◽  
Gated Channel ◽  
Two Peaks

A cyclic nucleotide-gated channel present in skeletal muscle plasma membrane has previously been identified as being responsible for insulin-activated sodium entry into muscle cells (J. E. M. McGeoch and G. Guidotti. J. Biol. Chem. 267:832-841, 1992). We have isolated this channel activity to further study and characterize it. The channel was solubilized from rabbit skeletal muscle sarcolemma and functionally reconstituted into phospholipid vesicles, as assayed by patch-clamp analysis of the reconstituted proteins. Channel activity was isolated by 8-bromo-guanosine 3',5'-cyclic monophosphate affinity chromatography, producing two distinct peaks of cyclic nucleotide-gated channel activity. These two types of channel activity differ in guanosine 3',5'-cyclic monophosphate affinity and in the ability to be opened by adenosine 3',5'-cyclic monophosphate. The cyclic nucleotide-gated channel from rod outer segments also forms two peaks of activity when purified in this manner. The presence of two forms of channel activity could have implications for the mechanism of insulin-activated sodium entry.

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