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https://www.readbyqxmd.com/read/28194973/implications-for-the-light-driven-chloride-ion-transport-mechanism-of-nonlabens-marinus-rhodopsin-3-by-its-photochemical-characteristics
#1
Takashi Tsukamoto, Susumu Yoshizawa, Takashi Kikukawa, Makoto Demura, Yuki Sudo
Several new retinal-based photoreceptor proteins that act as light-driven electrogenic halide ion pumps have recently been discovered. Some of them, called "NTQ" rhodopsins, contain a conserved Asn-Thr-Gln motif in the 3(rd) or C-helix. In this study, we investigated the photochemical characteristics of a NTQ rhodopsin, Nonlabens marinus rhodopsin 3 (NM-R3), which was discovered in the N. marinus S1-08(T) strain, using static and time-resolved spectroscopic techniques. We demonstrate that NM-R3 binds a Cl(-) in the vicinity of the retinal chromophore accompanied by a spectral blue shift from 568 nm in the absence of Cl(-) to 534 nm in the presence of Cl(-)...
February 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28186874/spontaneous-activation-of-visual-pigments-in-relation-to-openness-closedness-of-chromophore-binding-pocket
#2
Wendy Wing Sze Yue, Rikard Frederiksen, Xiaozhi Ren, Dong-Gen Luo, Takahiro Yamashita, Yoshinori Shichida, M Carter Cornwall, King-Wai Yau
Visual pigments can be spontaneously activated by internal thermal energy, generating noise that interferes with real-light detection. Recently, we developed a physicochemical theory that successfully predicts the rate of spontaneous activity of representative rod and cone pigments from their peak-absorption wavelength (λmax), with pigments having longer λmax being noisier. Interestingly, cone pigments may generally be ~25 fold noisier than rod pigments of the same λmax, possibly ascribed to an 'open' chromophore-binding pocket in cone pigments defined by the capability of chromophore-exchange in darkness...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28165484/new-insights-on-signal-propagation-by-sensory-rhodopsin-ii-transducer-complex
#3
A Ishchenko, E Round, V Borshchevskiy, S Grudinin, I Gushchin, J P Klare, A Remeeva, V Polovinkin, P Utrobin, T Balandin, M Engelhard, G Büldt, V Gordeliy
The complex of two membrane proteins, sensory rhodopsin II (NpSRII) with its cognate transducer (NpHtrII), mediates negative phototaxis in halobacteria N. pharaonis. Upon light activation NpSRII triggers a signal transduction chain homologous to the two-component system in eubacterial chemotaxis. Here we report on crystal structures of the ground and active M-state of the complex in the space group I212121. We demonstrate that the relative orientation of symmetrical parts of the dimer is parallel ("U"-shaped) contrary to the gusset-like ("V"-shaped) form of the previously reported structures of the NpSRII/NpHtrII complex in the space group P21212, although the structures of the monomers taken individually are nearly the same...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154160/tubby-family-proteins-are-adapters-for-ciliary-trafficking-of-integral-membrane-proteins
#4
Hemant B Badgandi, Sun-Hee Hwang, Issei S Shimada, Evan Loriot, Saikat Mukhopadhyay
The primary cilium is a paradigmatic organelle for studying compartmentalized signaling; however, unlike soluble protein trafficking, processes targeting integral membrane proteins to cilia are poorly understood. In this study, we determine that the tubby family protein TULP3 functions as a general adapter for ciliary trafficking of structurally diverse integral membrane cargo, including multiple reported and novel rhodopsin family G protein-coupled receptors (GPCRs) and the polycystic kidney disease-causing polycystin 1/2 complex...
February 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28151698/immunocytochemical-profiling-of-cultured-mouse-primary-retinal-cells
#5
Marina C Zalis, Sebastian Johansson, Ulrica Englund-Johansson
Primary retinal cell cultures and immunocytochemistry are important experimental platforms in ophthalmic research. Translation of retinal cells from their native environment to the in vitro milieu leads to cellular stress, jeopardizing their in vivo phenotype features. Moreover, the specificity and stability of many retinal immunochemical markers are poorly evaluated in retinal cell cultures. Hence, we here evaluated the expression profile of 17 retinal markers, that is, recoverin, rhodopsin, arrestin, Chx10, PKC, DCX, CRALBP, GS, vimentin, TPRV4, RBPMS, Brn3a, β-tubulin III, NeuN, MAP2, GFAP, and synaptophysin...
January 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28149772/differentiation-potential-of-human-adipose-tissue-derived-stem-cells-into-photoreceptors-through-explants-culture-and-enzyme-methods
#6
Wei-Wei Xu, Li Huang, Kelvin K L Chong, Doreen S Y Leung, Benjamin F L Li, Zheng-Qin Yin, Yi-Fei Huang, Chi Pui Pang
AIM: To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells (ADSCs) generated by enzyme (EN) and explant (EX) culture methods. METHODS: We investigated potentials of human orbital ADSCs to differentiate into photoreceptors through EN and EX culture methods. EN and EX orbital ADSCs were obtained from the same donor during rehabilitative orbital decompression, and then were subject to a 3-step induction using Noggin, DKK-1, IGF-1 and b-FGF at different time points for 38d...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28129424/formation-and-clearance-of-all-trans-retinol-in-rods-investigated-in-the-living-primate-eye-with-two-photon-ophthalmoscopy
#7
Robin Sharma, Christina Schwarz, Jennifer J Hunter, Grazyna Palczewska, Krzysztof Palczewski, David R Williams
Purpose: Two-photon excited fluorescence (TPEF) imaging has potential as a functional tool for tracking visual pigment regeneration in the living eye. Previous studies have shown that all-trans-retinol is likely the chief source of time-varying TPEF from photoreceptors. Endogenous TPEF from retinol could provide the specificity desired for tracking the visual cycle. However, in vivo characterization of native retinol kinetics is complicated by visual stimulation from the imaging beam...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28123034/opposing-effects-of-valproic-acid-treatment-mediated-by-histone-deacetylase-inhibitor-activity-in-four-transgenic-x-laevis-models-of-retinitis-pigmentosa
#8
Ruanne Y J Vent-Schmidt, Runxia H Wen, Zusheng Zong, Colette N Chiu, Beatrice M Tam, Christopher G May, Orson L Moritz
: Retinitis pigmentosa (RP) is an inherited retinal degeneration (RD) that leads to blindness for which no treatment is available. RP is frequently caused by mutations in Rhodopsin; in some animal models, RD is exacerbated by light. Valproic acid (VPA) is a proposed treatment for RP and other neurodegenerative disorders, with a phase II trial for RP under way. However, the therapeutic mechanism is unclear, with minimal research supporting its use in RP. We investigated the effects of VPA on Xenopus laevis models of RP expressing human P23H, T17M, T4K, and Q344ter rhodopsins, which are associated with RP in humans...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28118669/the-ciliopathy-gene-ahi1-is-required-for-zebrafish-cone-photoreceptor-outer-segment-morphogenesis-and-survival
#9
Emma M Lessieur, Joseph Fogerty, Robert J Gaivin, Ping Song, Brian D Perkins
Purpose: Joubert syndrome (JBTS) is an autosomal recessive ciliopathy with considerable phenotypic variability. In addition to central nervous system abnormalities, a subset of JBTS patients exhibit retinal dystrophy and/or kidney disease. Mutations in the AHI1 gene are causative for approximately 10% of all JBTS cases. The purpose of this study was to generate ahi1 mutant alleles in zebrafish and to characterize the retinal phenotypes. Methods: Zebrafish ahi1 mutants were generated using transcription activator-like effector nucleases (TALENs)...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28114588/acute-and-protracted-cell-death-in-light-induced-retinal-degeneration-in-the-canine-model-of-rhodopsin-autosomal-dominant-retinitis-pigmentosa
#10
Raghavi Sudharsan, Kristina M Simone, Nathan P Anderson, Gustavo D Aguirre, William A Beltran
Purpose: To characterize a light damage paradigm and establish structural and immunocytochemical measures of acute and protracted light-induced retinal degeneration in the rhodopsin (RHO) T4R dog model of RHO-autosomal dominant retinitis pigmentosa (ADRP). Methods: Retinal light damage was induced in mutant dogs with a 1-minute exposure to various light intensities (0.1-1.0 mW/cm2) delivered with a Ganzfeld stimulator, or by fundus photography. Photoreceptor cell death was assessed by TUNEL assay, and alterations in retinal layers were examined by histology and immunohistochemistry 24 hours and 2 weeks after light exposure...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28112220/the-natural-retinoprotectant-chrysophanol-attenuated-photoreceptor-cell-apoptosis-in-an-n-methyl-n-nitrosourea-induced-mouse-model-of-retinal-degenaration
#11
Fan-Li Lin, Cheng-Hui Lin, Jau-Der Ho, Jing-Lun Yen, Hung-Ming Chang, George C Y Chiou, Yu-Wen Cheng, George Hsiao
Retinitis pigmentosa (RP) is an inherited photoreceptor-degenerative disease, and neuronal degeneration in RP is exacerbated by glial activation. Cassia seed (Jue-ming-zi) is a traditional herbal medicine commonly used to treat ocular diseases in Asia. In this report, we investigated the retina-protective effect of chrysophanol, an active component of Cassia seed, in an N-methyl-N-nitrosourea (MNU)-induced mouse model of RP. We determined that chrysophanol inhibited the functional and morphological features of MNU-induced retinal degeneration using scotopic electroretinography (ERG), optical coherence tomography (OCT), and immunohistochemistry analysis of R/G opsin and rhodopsin...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103783/understanding-corticotropin-releasing-factor-receptor-crfr-activation-using-structural-models
#12
Arnau Cordomi, George Liapakis, Minos Timotheos Matsoukas
The corticotropin-releasing factor type 1 and 2 receptors (CRF1R and CRF2R) belong to the secretin-like family, also known as class B1, of G protein-coupled receptors (GPCRs). Several endogenous hormones mediate their responses through the CRF receptors, such as CRF and the urocortins. The structures for the N-terminus extracellular domain of both CRF1R and CRF2R in complex with peptidic ligands were released a few years ago and permitted the study of hormone binding to the orthosteric binding site. It was not until more recently, when the crystal structure of the transmembrane domain of human CRF1R in its inactive state bound to an allosteric antagonist became available...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28094925/retinal-based-proton-pumping-in-the-near-infrared
#13
Srividya Ganapathy, Hanka Venselaar, Que Chen, Huub J M de Groot, Klaas J Hellingwerf, Willem J de Grip
Proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) are retinal-based light-driven proton pumps that absorb visible light (maxima at 520-540 nm). Shifting the action spectra of these proton pumps beyond 700 nm would generate new prospects in optogenetics, membrane sensor technology, and complementation of oxygenic phototrophy. We therefore investigated the effect of red-shifting analogues of retinal, combined with red-shifting mutations, on the spectral properties and pump activity of the resulting pigments...
February 2, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28089451/crystallogenesis-of-membrane-proteins-mediated-by-polymer-bounded-lipid-nanodiscs
#14
Jana Broecker, Bryan T Eger, Oliver P Ernst
For some membrane proteins, detergent-mediated solubilization compromises protein stability and functionality, often impairing biophysical and structural analyses. Hence, membrane-protein structure determination is a continuing bottleneck in the field of protein crystallography. Here, as an alternative to approaches mediated by conventional detergents, we report the crystallogenesis of a recombinantly produced membrane protein that never left a lipid bilayer environment. We used styrene-maleic acid (SMA) copolymers to solubilize lipid-embedded proteins into SMA nanodiscs, purified these discs by affinity and size-exclusion chromatography, and transferred proteins into the lipidic cubic phase (LCP) for in meso crystallization...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/28088625/absence-of-dj-1-causes-age-related-retinal-abnormalities-in-association-with-increased-oxidative-stress
#15
Vera L Bonilha, Brent A Bell, Mary E Rayborn, Ivy S Samuels, Anna King, Joe G Hollyfield, Chengsong Xie, Huaibin Cai
Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28087932/the-complexity-of-fungal-vision
#16
Reinhard Fischer, Jesus Aguirre, Alfredo Herrera-Estrella, Luis M Corrochano
Life, as we know it, would not be possible without light. Light is not only a primary source of energy, but also an important source of information for many organisms. To sense light, only a few photoreceptor systems have developed during evolution. They are all based on an organic molecule with conjugated double bonds that allows energy transfer from visible (or UV) light to its cognate protein to translate the primary physical photoresponse to cell-biological actions. The three main classes of receptors are flavin-based blue-light, retinal-based green-light (such as rhodopsin), and linear tetrapyrrole-based red-light sensors...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28076806/measurement-of-slow-spontaneous-release-of%C3%A2-11-cis-retinal-from-rhodopsin
#17
He Tian, Thomas P Sakmar, Thomas Huber
The vertebrate visual photoreceptor rhodopsin (Rho) is a unique G protein-coupled receptor as it utilizes a covalently tethered inverse agonist (11-cis-retinal) as the native ligand. Previously, electrophysiological studies showed that ligand binding of 11-cis-retinal in dark-adapted Rho was essentially irreversible with a half-life estimated to be 420 years, until after thermal isomerization to all-trans-retinal, which then slowly dissociates. This long lifetime of 11-cis-retinal binding was considered to be physiologically important for minimizing background signal (dark noise) of the visual system...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28073248/interplay-of-g-protein-coupled-receptors-with-the-membrane-insights-from-supra-atomic-coarse-grain-molecular-dynamics-simulations
#18
Xavier Periole
G protein-coupled receptors (GPCRs) are central to many fundamental cellular signaling pathways. They transduce signals from the outside to the inside of cells in physiological processes ranging from vision to immune response. It is extremely challenging to look at them individually using conventional experimental techniques. Recently, a pseudo atomistic molecular model has emerged as a valuable tool to access information on GPCRs, more specifically on their interactions with their environment in their native cell membrane and the consequences on their supramolecular organization...
January 11, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28072545/ultrafast-photoinduced-deactivation-dynamics-of-proteorhodopsin
#19
C Elias Eckert, Jagdeep Kaur, Clemens Glaubitz, Josef Wachtveitl
We report femtosecond time-resolved absorption change measurements of the photoinduced deactivation dynamics of a microbial rhodopsin in the ultraviolet-visible and mid-infrared range. The blue light quenching process is recorded in green proteorhodopsin's (GPR) primary proton donor mutant E108Q from the deprotonated 13-cis photointermediate. The return of GPR to the dark state occurs in two steps, starting with the photoinduced 13-cis to all-trans reisomerization of the retinal. The subsequent Schiff base reprotonation via the primary proton acceptor (D97) occurs on a nanosecond time scale...
January 19, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28065882/rescue-of-mutant-rhodopsin-traffic-by-metformin-induced-ampk-activation-accelerates-photoreceptor-degeneration
#20
Dimitra Athanasiou, Monica Aguila, Chikwado A Opefi, Kieron South, James Bellingham, Dalila Bevilacqua, Peter M Munro, Naheed Kanuga, Francesca E Mackenzie, Adam M Dubis, Anastasios Georgiadis, Anna B Graca, Rachael A Pearson, Robin R Ali, Sanae Sakami, Krzysztof Palczewski, Michael Y Sherman, Philip J Reeves, Michael E Cheetham
Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death...
January 7, 2017: Human Molecular Genetics
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