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Maite Ogueta, Roger C Hardie, Ralf Stanewsky
The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction...
April 30, 2018: Current Biology: CB
Byeongho Park, Heehong Yang, Tai Hwan Ha, Hyun Seo Park, Seung Ja Oh, Yong-Sang Ryu, Youngho Cho, Hyo-Suk Kim, Juyeong Oh, Dong Kyu Lee, Chulki Kim, Taikjin Lee, Minah Seo, Jaebin Choi, Young Min Jhon, Deok Ha Woo, Seok Lee, Seok Hwan Kim, Hyuk-Jae Lee, Seong Chan Jun, Hyun Seok Song, Tai Hyun Park, Jae Hun Kim
Photosensitive materials contain biologically engineered elements and are constructed using delicate techniques, with special attention devoted to efficiency, stability, and biocompatibility. However, to date, no photosensitive material has been developed to replace damaged visual-systems to detect light and transmit the signal to a neuron in the human body. In the current study, artificial nanovesicle-based photosensitive materials are observed to possess the characteristics of photoreceptors similar to the human eye...
May 18, 2018: Advanced Materials
Yuanyuan Chen, Yu Chen, Beata Jastrzebska, Marcin Golczak, Sahil Gulati, Hong Tang, William Seibel, Xiaoyu Li, Hui Jin, Yong Han, Songqi Gao, Jianye Zhang, Xujie Liu, Hossein Heidari-Torkabadi, Phoebe L Stewart, William E Harte, Gregory P Tochtrop, Krzysztof Palczewski
Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity...
May 17, 2018: Nature Communications
Maurizio Morri, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J Gerrard, Priscila P Hirschfeld, Jan Schwarz, Harald Janovjak
G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+ -, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors...
May 16, 2018: Nature Communications
Yi-Ting Tsai, Wen-Hsuan Wu, Ting-Ting Lee, Wei-Pu Wu, Christine L Xu, Karen S Park, Xuan Cui, Sally Justus, Chyuan-Sheng Lin, Ruben Jauregui, Pei-Yin Su, Stephen H Tsang
PURPOSE: To develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin (RHO). DESIGN: Experimental study for a combination gene therapy that uses both gene ablation and gene replacement. PARTICIPANTS: This study included 2 kinds of human RHO mutation knock-in mouse models: RhoP23H and RhoD190N . In total, 23 RhoP23H/P23H , 43 RhoP23H/+ , and 31 RhoD190N/+ mice were used for analysis...
May 5, 2018: Ophthalmology
Jacob G Sivak, Jeremy M Sivak
It has been speculated that the unitary eyes of vertebrates and molluscs, and the compound eyes of insects and crustaceans, evolved separately. On the other hand, the common use of rhodopsin as a photoreceptor molecule, and the conservation of Pax6 as a master control gene for eye development, suggest instead that the eye evolved once. Yet, recently the molecular genetics that had seemed to suggest a definitive answer to this evolutionary point has once again become cloudy. Here we propose an alternative approach to addressing the question of eye evolution through comparative analyses of physiological optics...
May 11, 2018: Experimental Eye Research
Riho Takayama, Akimasa Kaneko, Takashi Okitsu, Satoshi P Tsunoda, Kazumi Shimono, Misao Mizuno, Keiichi Kojima, Takashi Tsukamoto, Hideki Kandori, Yasuhisa Mizutani, Akimori Wada, Yuki Sudo
Rhodopsin is widely distributed in organisms as a membrane-embedded photoreceptor protein, consisting of the apoprotein opsin and vitamin-A aldehyde retinal, A1-retinal and A2-retinal being the natural chromophores. Modifications of opsin (e.g., by mutations) have provided insights into the molecular mechanism of the light-induced functions of rhodopsins as well as providing tools in chemical biology to control cellular activity by light. Instead of the apoprotein opsin, in this study, we focused on the retinal chromophore and synthesized three vinylene derivatives of A2-retinal...
May 11, 2018: Journal of Physical Chemistry Letters
Hwa Sun Kim, Andrew Vargas, Yun Sung Eom, Justin Li, Kyra L Yamamoto, Cheryl Mae Craft, Eun-Jin Lee
Retinitis pigmentosa (RP), an inherited retinal degenerative disease, is characterized by a progressive loss of rod photoreceptors followed by loss of cone photoreceptors. Previously, when tissue inhibitor of metalloproteinase 1 (TIMP1), a key extracellular matrix (ECM) regulator that binds to and inhibits activation of Matrix metallopeptidase 9 (MMP9) was intravitreal injected into eyes of a transgenic rhodopsin rat model of RP, S334ter-line3, we discovered cone outer segments are partially protected. In parallel, we reported that a specific MMP9 and MMP2 inhibitor, SB-3CT, interferes with mechanisms leading to rod photoreceptor cell death in an MMP9 dependent manner...
2018: PloS One
Haifang Zhao, Jing Wang, Tao Wang
Synthesis and maturation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and for photoreceptor homeostasis. In Drosophila, the main rhodopsin, Rh1, is synthesized in the endoplasmic reticulum and transported to the rhabdomere through the secretory pathway. In an unbiased genetic screen for factors involved in rhodopsin homeostasis, we identified mutations in vha68-1, which encodes V-ATPase catalytic subunit A isoform 1 of the V1 component. Loss of vha68-1 in photoreceptor cells disrupted post-Golgi anterograde trafficking of Rh1, reduced light sensitivity, increased secretory vesicle pH, and resulted in incomplete Rh1 deglycosylation...
May 9, 2018: Molecular Biology of the Cell
Emanuel Pfitzner, Hirofumi Seki, Ramona Schlesinger, Kenichi Ataka, Joachim Heberle
Plasmonic surfaces have emerged as a powerful platform for biomolecular sensing applications and can be designed to optimize the plasmonic resonance for probing molecular vibrations at utmost sensitivity. Here, we present a facile procedure to generate metallic micro disc antenna arrays that are employed in surface-enhanced infrared absorption (SEIRA) spectroscopy of biomolecules. Transmission electron microscopy (TEM) grids are used as shadow mask deployed during physical vapor deposition of gold. The resulting disc-shaped antennas exhibit enhancement factors of the vibrational bands of 4×104 giving rise to a detection limit < 1 femtomol (10-15 mol) of molecules...
May 9, 2018: ACS Sensors
Sheerly Rodríguez, May-Li Silva, Gustavo Benaím, José Bubis
In order to monitor conformational changes following photoactivation and phosphorylation of bovine rhodopsin, the two reactive sulfhydryl groups at Cys140 and Cys316 were specifically labeled with the monobromobimane (mBBr) fluorophore. Although alterations in conformation after light exposure of rhodopsin were not detected by fluorescence excitation scans (300-450 nm) of the mBBr-labeled protein, the fluorescence signal was reduced ∼ 90% in samples containing photoactivated phosphorhodopsin. Predominant labeling at either Cys140 or Cys316 in light-activated and phosphorylated rhodopsin merely generated a decrease of ∼ 38% and 28%, respectively, in the fluorescence excitation intensity...
May 3, 2018: Biochimie
Glenn P Lobo, Gayle Pauer, Joshua H Lipschutz, Stephanie A Hagstrom
Vitamin A/retinol (ROL) and its metabolites (retinoids) play critical roles in eye development and photoreception. Short-term dietary vitamin A deficiency (VAD) manifests clinically as night blindness, while prolonged VAD is known to cause retinal pigment epithelium (RPE) and photoreceptor degeneration. Therefore, sustained uptake of dietary vitamin A, for ocular retinoid production, is essential for photoreceptor health and visual function. The mechanisms influencing the uptake, storage, and supply of dietary vitamin A, for ocular retinoid production, however, are not fully understood...
2018: Advances in Experimental Medicine and Biology
Ekaterina S Lobanova, Stella Finkelstein, Jing Li, Amanda M Travis, Ying Hao, Mikael Klingeborn, Nikolai P Skiba, Raymond J Deshaies, Vadim Y Arshavsky
Inherited retinal degenerations, affecting more than 2 million people worldwide, are caused by mutations in over 200 genes. This suggests that the most efficient therapeutic strategies would be mutation independent, i.e., targeting common pathological conditions arising from many disease-causing mutations. Previous studies revealed that one such condition is an insufficiency of the ubiquitin-proteasome system to process misfolded or mistargeted proteins in affected photoreceptor cells. We now report that retinal degeneration in mice can be significantly delayed by increasing photoreceptor proteasomal activity...
April 30, 2018: Nature Communications
Shinya Tahara, Satoshi Takeuchi, Rei Abe-Yoshizumi, Keiichi Inoue, Hiroyuki Ohtani, Hideki Kandori, Tahei Tahara
KR2 is the first light-driven Na+ -pumping rhodopsin discovered. It was reported that the photoexcitation of KR2 generates multiple S1 states, i.e., "reactive" and "nonreactive" S1 states at physiological pH, but their origin remained unclear. In this study, we examined the S1 state dynamics of KR2 using femtosecond time-resolved absorption spectroscopy at different pH's in the range from 4 to 11. It was found that the reactive S1 state is predominantly formed at pH >9, but its population drastically decreases with decreasing pH while the population of the nonreactive S1 state(s) increases...
April 30, 2018: Journal of Physical Chemistry. B
Julia A Maresca, Kelsey J Miller, Jessica L Keffer, Chandran R Sabanayagam, Barbara J Campbell
Although sunlight is an abundant source of energy in surface environments, less than 0.5% of the available photons are captured by (bacterio)chlorophyll dependent photosynthesis in plants and bacteria. Metagenomic data indicate that 30-60% of the bacterial genomes in some environments encode rhodopsins, retinal-based photosystems found in heterotrophs, suggesting that sunlight may provide energy for more life than previously suspected. However, quantitative data on the number of cells that produce rhodopsins in environmental systems is limited...
April 27, 2018: Applied and Environmental Microbiology
Marwa H Farag, Thomas L C Jansen, Jasper Knoester
In rhodopsin, the absorption of a photon causes the isomerization of the 11-cis isomer of the retinal chromophore to its all-trans isomer. This isomerization is known to occur through a conical intersection (CI) and the internal conversion through the CI is known to be vibrationally coherent. Recently measured two-dimensional electronic spectra (2DES) showed dramatic absorptive spectral features at early waiting times associated with the transition through the CI. The common two-state two-mode model Hamiltonian was unable to elucidate the origin of these features...
April 26, 2018: Physical Chemistry Chemical Physics: PCCP
Kim Potvin-Fournier, Geneviève Valois-Paillard, Marie-Claude Gagnon, Thierry Lefèvre, Pierre Audet, Line Cantin, Jean-François Paquin, Christian Salesse, Michèle Auger
Recoverin is a protein involved in the phototransduction cascade by regulating the activity of rhodopsin kinase through a calcium-dependent binding process at the surface of rod outer segment disk membranes. We have investigated the interaction of recoverin with zwitterionic phosphatidylcholine bilayers, the major lipid component of the rod outer segment disk membranes, using both 31 P and 19 F solid-state nuclear magnetic resonance (NMR) and infrared spectroscopy. In particular, several novel approaches have been used, such as the centerband-only detection of exchange (CODEX) technique to investigate lipid lateral diffusion and 19 F NMR to probe the environment of the recoverin myristoyl group...
April 24, 2018: European Biophysics Journal: EBJ
Jianmin Lu, Lingyu Luo, Deqiang Huang, Xian Liu, Xin Xia, Zhengying Wang, Byron L Lam, Jinglin Yi, Rong Wen, Yiwen Li
Retinal degenerations are a major cause of vision impairment and blindness. Neuroprotective therapy is a promising therapeutic strategy for retinal degenerative diseases. We investigated a novel neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in the retina. MANF is expressed at a high level during postnatal development and the expression declines to a lower level as the retina matures. Müller cells are the major cells expressing MANF. It is also found in the retinal ganglion cells, in the inner nuclear layer (INL) neurons, and in retinal pigment epithelial (RPE) cells...
March 2018: ENeuro
Vasiliy I Vladimirov, Evgeni Yu Zernii, Viktoriia E Baksheeva, Hanna Wimberg, Alexey S Kazakov, Natalya K Tikhomirova, Ekaterina L Nemashkalova, Vladimir A Mitkevich, Andrey A Zamyatnin, Valery M Lipkin, Pavel P Philippov, Sergei E Permyakov, Ivan I Senin, Karl-W Koch, Dmitry V Zinchenko
Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca2+ -binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners...
April 14, 2018: Cell Calcium
Jun Tamogami, Takashi Kikukawa, Keisuke Ohkawa, Noboru Ohsawa, Toshifumi Nara, Makoto Demura, Seiji Miyauchi, Tomomi Kimura-Someya, Mikako Shirouzu, Shigeyuki Yokoyama, Kazumi Shimono, Naoki Kamo
Acetabularia rhodopsin II (ARII or Ace2), an outward light-driven algal proton pump found in the giant unicellular marine alga Acetabularia acetabulum, has a unique property in the cytoplasmic (CP) side of its channel. The X-ray crystal structure of ARII in a dark state suggested the formation of an interhelical hydrogen bond between C218ARII and D92ARII , an internal proton donor to the Schiff base (Wada et al., 2011). In this report, we investigated the photocycles of two mutants at position C218ARII : C218AARII which disrupts the interaction with D92ARII , and C218SARII which potentially forms a stronger hydrogen bond...
April 11, 2018: Journal of Photochemistry and Photobiology. B, Biology
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