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https://www.readbyqxmd.com/read/28495882/endoplasmic-reticulum-er-ca-2-channel-activity-contributes-to-er-stress-and-cone-death-in-cyclic-nucleotide-gated-channel-deficiency
#1
Michael R Butler, Hongwei Ma, Fan Yang, Joshua Belcher, Yun-Zheng Le, Katsuhiko Mikoshiba, Martin Biel, Stylianos Michalakis, Anthony Iuso, David Krizaj, Xi-Qin Ding
Endoplasmic reticulum (ER) stress and mislocalization of improperly folded proteins have been shown to contribute to photoreceptor death in models of inherited retinal degenerative diseases. In particular, mice with cone cyclic nucleotide-gated (CNG) channel deficiency, a model for achromatopsia, display both early-onset ER stress and opsin mistrafficking. By 2 weeks, these mice show elevated signaling from all three arms of the ER stress pathway, and by 1 month, cone opsin is improperly distributed away from its normal outer segment location to other retinal layers...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28396445/cryoem-structure-of-a-prokaryotic-cyclic-nucleotide-gated-ion-channel
#2
Zachary M James, Andrew J Borst, Yoni Haitin, Brandon Frenz, Frank DiMaio, William N Zagotta, David Veesler
Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxyl-terminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28379353/two-pathways-of-rod-photoreceptor-cell-death-induced-by-elevated-cgmp
#3
Tian Wang, Stephen H Tsang, Jeannie Chen
Cyclic-GMP is a second messenger in phototransduction, a G-protein signaling cascade that conveys photon absorption by rhodopsin to a change in current at the rod photoreceptor outer segment plasma membrane. Basal cGMP level is strictly controlled by the opposing actions of phosphodiesterase (PDE6) and retinal guanylyl cyclases (GCs), and mutations in genes that disrupt cGMP homeostasis leads to retinal degeneration in humans through mechanisms that are incompletely understood. The purpose of this study is to examine two distinct cellular targets of cGMP: the cGMP-gated (CNG) channels and protein kinase G (PRKG), and how each may contribute to rod cell death...
April 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28279024/contribution-of-the-cyclic-nucleotide-gated-channel-subunit-cng-3-to-olfactory-plasticity-in-caenorhabditis-elegans
#4
Damien M O'Halloran, Svetlana Altshuler-Keylin, Xiao-Dong Zhang, Chao He, Christopher Morales-Phan, Yawei Yu, Julia A Kaye, Chantal Brueggemann, Tsung-Yu Chen, Noelle D L'Etoile
In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28134524/monod-wyman-changeux-analysis-of-ligand-gated-ion-channel-mutants
#5
Tal Einav, Rob Phillips
We present a framework for computing the gating properties of ligand-gated ion channel mutants using the Monod-Wyman-Changeux (MWC) model of allostery. We derive simple analytic formulas for key functional properties such as the leakiness, dynamic range, half-maximal effective concentration ([EC50]), and effective Hill coefficient, and explore the full spectrum of phenotypes that are accessible through mutations. Specifically, we consider mutations in the channel pore of nicotinic acetylcholine receptor (nAChR) and the ligand binding domain of a cyclic nucleotide-gated (CNG) ion channel, demonstrating how each mutation can be characterized as only affecting a subset of the biophysical parameters...
April 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28095637/gene-therapy-for-achromatopsia
#6
REVIEW
Stylianos Michalakis, Christian Schön, Elvir Becirovic, Martin Biel
AIM: This review summarizes the current status of Achromatopsia (ACHM) gene therapy-related research activities and provides an outlook for their clinical application. DISCUSSION: ACHM is an inherited eye disease characterized by congenital absence of cone photoreceptor function. As a consequence, ACHM is associated with strongly impaired daylight vision, photophobia, nystagmus, and lack of color discrimination. Currently, six genes have been linked to ACHM. Up to 80% of the patients carry mutations in the genes CNGA3 and CNGB3 encoding the two subunits of the cone cyclic nucleotide-gated (CNG) channel...
January 17, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28075020/adenosine-receptors-regulate-gap-junction-coupling-of-the-human-cerebral-microvascular-endothelial-cells-hcmec-d3-by-ca-2-influx-through-cyclic-nucleotide-gated-channels
#7
Almke Bader, Willem Bintig, Daniela Begandt, Anne Klett, Ina G Siller, Carola Gregor, Frank Schaarschmidt, Babette Weksler, Ignacio Romero, Pierre-Olivier Couraud, Stefan W Hell, Anaclet Ngezahayo
KEY POINTS: Gap junction channels are essential for the formation and regulation of physiological units in tissues by allowing the lateral cell-to-cell diffusion of ions, metabolites and second messengers. Stimulation of the adenosine receptor subtype A2B increases the gap junction coupling in the human blood-brain barrier endothelial cell line hCMEC/D3. Although the increased gap junction coupling is cAMP-dependent, neither the protein kinase A nor the exchange protein directly activated by cAMP were involved in this increase...
April 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28053034/simultaneous-loss-of-nckx4-and-cng-channel-desensitization-impairs-olfactory-sensitivity
#8
Christopher H Ferguson, Haiqing Zhao
In vertebrate olfactory sensory neurons (OSNs), Ca(2+) plays key roles in both mediating and regulating the olfactory response. Ca(2+) enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca(2+)-activated chloride channel to amplify the response. Ca(2+) also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca(2+)/calmodulin (CaM), to reduce the response...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27647918/cyclic-nucleotide-gated-cation-current-and-ca2-activated-cl-current-elicited-by-odorant-in-vertebrate-olfactory-receptor-neurons
#9
Rong-Chang Li, Yair Ben-Chaim, King-Wai Yau, Chih-Chun Lin
Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide-gated (CNG), nonselective cation channels. The consequent Ca(2+) influx triggers adaptation but also signal amplification, the latter by opening a Ca(2+)-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27580676/the-na-ca-2-k-exchanger-2-modulates-mammalian-cone-phototransduction
#10
Keisuke Sakurai, Frans Vinberg, Tian Wang, Jeannie Chen, Vladimir J Kefalov
Calcium ions (Ca(2+)) modulate the phototransduction cascade of vertebrate cone photoreceptors to tune gain, inactivation, and light adaptation. In darkness, the continuous current entering the cone outer segment through cGMP-gated (CNG) channels is carried in part by Ca(2+), which is then extruded back to the extracellular space. The mechanism of Ca(2+) extrusion from mammalian cones is not understood. The dominant view has been that the cone-specific isoform of the Na(+)/Ca(2+), K(+) exchanger, NCKX2, is responsible for removing Ca(2+) from their outer segments...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27561605/the-cyclic-nucleotide-gated-channel-subunit-cng-1-instructs-behavioral-outputs-in-caenorhabditis-elegans-by-coincidence-detection-of-nutritional-status-and-olfactory-input
#11
Chao He, Svetlana Altshuler-Keylin, David Daniel, Noelle D L'Etoile, Damien O'Halloran
In mammals, olfactory subsystems have been shown to express seven-transmembrane G-protein-coupled receptors (GPCRs) in a one-receptor-one-neuron pattern, whereas in Caenorhabditis elegans, olfactory sensory neurons express multiple G-protein coupled odorant receptors per olfactory sensory neuron. In both mammalian and C. elegans olfactory sensory neurons (OSNs), the process of olfactory adaptation begins within the OSN; this process of negative feedback within the mammalian OSN has been well described in mammals and enables activated OSNs to desensitize their response cell autonomously while attending to odors detected by separate OSNs...
October 6, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27405959/deciphering-the-function-of-the-cngb1b-subunit-in-olfactory-cng-channels
#12
Vasilica Nache, Nisa Wongsamitkul, Jana Kusch, Thomas Zimmer, Frank Schwede, Klaus Benndorf
Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27353446/patch-clamp-fluorometry-based-channel-counting-to-determine-hcn-channel-conductance
#13
Chang Liu, Changan Xie, Khade Grant, Zhuocheng Su, Weihua Gao, Qinglian Liu, Lei Zhou
Counting ion channels on cell membranes is of fundamental importance for the study of channel biophysics. Channel counting has thus far been tackled by classical approaches, such as radioactive labeling of ion channels with blockers, gating current measurements, and nonstationary noise analysis. Here, we develop a counting method based on patch-clamp fluorometry (PCF), which enables simultaneous electrical and optical recordings, and apply it to EGFP-tagged, hyperpolarization-activated and cyclic nucleotide-regulated (HCN) channels...
July 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27270916/cav1-4-l-type-calcium-channels-contribute-to-calpain-activation-in-degenerating-photoreceptors-of-rd1-mice
#14
Christian Schön, François Paquet-Durand, Stylianos Michalakis
Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG) channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC). Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa...
2016: PloS One
https://www.readbyqxmd.com/read/27207328/differential-expression-of-axon-sorting-molecules-in%C3%A2-mouse-olfactory-sensory-neurons
#15
Naoki Ihara, Ai Nakashima, Naosuke Hoshina, Yuji Ikegaya, Haruki Takeuchi
In the mouse olfactory system, the axons of olfactory sensory neurons that express the same type of odorant receptor (OR) converge to a specific set of glomeruli in the olfactory bulb (OB). It is widely accepted that expressed OR molecules instruct glomerular segregation by regulating the expression of axon-sorting molecules. Although the relationship between the expression of axon-sorting molecules and OR types has been analyzed in detail, those between the expressions of axon-sorting molecules remain to be elucidated...
August 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27115025/optimization-of-camp-fluorescence-dataset-from-actone-cannabinoid-receptor-1-cell-line
#16
Chaela S Presley, Ammaar H Abidi, Bob M Moore
The ACTOne cannabinoid receptor 1 functional system is comprised of transfected HEK cells with the parental cyclic nucleotide gated channel (CNG) co-transfected with cannabinoid receptor 1 (CB1). The ACTOne CB1 cell line was evaluated for cAMP driven fluorescence by optimizing experimental conditions for sensitivity to forskolin and CP 55,940, reading time point, reliability of cell passage number, and pertussis inactivation of Gi/o.
June 2016: Data in Brief
https://www.readbyqxmd.com/read/27113933/single-ca-2-activated-cl-channel-currents-recorded-from-toad-olfactory-cilia
#17
Ricardo Delgado, Casilda V Mura, Juan Bacigalupo
BACKGROUND: Odor transduction, occurring in the chemosensory cilia of vertebrate olfactory sensory neurons, is triggered by guanosine triphosphate-coupled odor receptors and mediated by a cyclic adenosine monophosphate (cAMP) signaling cascade, where cAMP opens cationic non-selective cyclic nucleotide-gated (CNG) channels. Calcium enters through CNG gates Ca(2+)-activated Cl(-) channels, allowing a Cl(-) inward current that enhances the depolarization initiated by the CNG-dependent inward current...
2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27065801/identification-of-a-novel-gnao-mediated-alternate-olfactory-signaling-pathway-in-murine-osns
#18
Paul Scholz, Julia Mohrhardt, Fabian Jansen, Benjamin Kalbe, Claudia Haering, Katharina Klasen, Hanns Hatt, Sabrina Osterloh
It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG) and at least one other known weak Olfr73 agonist (Raspberry Ketone) trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/26969165/regulation-of-cnga1-channel-gating-by-interactions-with-the-membrane
#19
Teresa K Aman, Sharona E Gordon, William N Zagotta
Cyclic nucleotide-gated (CNG) channels are expressed in rod photoreceptors and open in response to direct binding of cyclic nucleotides. We have previously shown that potentiation of CNGA1 channels by transition metals requires a histidine in the A' helix following the S6 transmembrane segment. Here, we used transition metal ion FRET and patch clamp fluorometry with a fluorescent, noncanonical amino acid (3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap)) to show that the potentiating transition metal Co(2+) binds in or near the A' helix...
May 6, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26893377/the-b3-subunit-of-the-cone-cyclic-nucleotide-gated-channel-regulates-the-light-responses-of-cones-and-contributes-to-the-channel-structural-flexibility
#20
Xi-Qin Ding, Arjun Thapa, Hongwei Ma, Jianhua Xu, Michael H Elliott, Karla K Rodgers, Marci L Smith, Jin-Shan Wang, Steven J Pittler, Vladimir J Kefalov
Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability...
April 15, 2016: Journal of Biological Chemistry
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