Relaxed Selective Constraints Drove Functional Modifications In
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The Vertebrate Retina Contains Two Types of Photoreceptors: Rods That
JOURNAL OF NEUROCHEMISTRY | 2009 | 108 | 91–101 doi: 10.1111/j.1471-4159.2008.05739.x *Department of Anatomy, School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan Genetics and Development Division, Toronto Western Research Institute, University Health Network, Department of Ophthalmology and Visual Sciences and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada àUniversity of Ottawa Eye Institute and Ottawa Health Research Institute, Ottawa, Ontario, Canada Abstract The retinas of staggerer mice, carrying a null mutation of Color vision is supported by retinal cone photoreceptors that, RORa, show significant down-regulation of Opn1sw, in most mammals, express two photopigments sensitive to Opn1mw, and Arr3. RORa acts in synergy with cone-rod short (S-opsin) or middle (M-opsin) wavelengths. Expression homeobox transcription factor (Crx), to activate the Opn1sw of the Opn1sw and Opn1mw genes, encoding S-opsin and promoter in vitro. Chromatin immunoprecipitation assays re- M-opsin, respectively, is under the control of nuclear veal that RORa directly binds to the Opn1sw promoter, receptors, including thyroid hormone receptor b2 (TRb2), Opn1mw locus control region, and the Arr3 promoter in vivo. retinoid X receptor c (RXRc), and RORb, a member of the Our data suggest that RORa plays a crucial role in cone retinoic acid receptor-related orphan receptor (ROR) family. development by directly regulating multiple cone genes. We now demonstrate that RORa, another member of the ROR Keywords: arrestin, cone photoreceptor, opsin, retina, family, regulates Opn1sw, Opn1mw, as well as Arr3 (cone RORa, staggerer. arrestin) in the mouse retina. RORa expression is detected in J. -
Investigating Cone Photoreceptor Development Using Patient-Derived NRL Null Retinal Organoids
ARTICLE https://doi.org/10.1038/s42003-020-0808-5 OPEN Investigating cone photoreceptor development using patient-derived NRL null retinal organoids Alyssa Kallman1,11, Elizabeth E. Capowski 2,11, Jie Wang 3, Aniruddha M. Kaushik4, Alex D. Jansen2, Kimberly L. Edwards2, Liben Chen4, Cynthia A. Berlinicke3, M. Joseph Phillips2,5, Eric A. Pierce6, Jiang Qian3, ✉ ✉ Tza-Huei Wang4,7, David M. Gamm2,5,8 & Donald J. Zack 1,3,9,10 1234567890():,; Photoreceptor loss is a leading cause of blindness, but mechanisms underlying photoreceptor degeneration are not well understood. Treatment strategies would benefit from improved understanding of gene-expression patterns directing photoreceptor development, as many genes are implicated in both development and degeneration. Neural retina leucine zipper (NRL) is critical for rod photoreceptor genesis and degeneration, with NRL mutations known to cause enhanced S-cone syndrome and retinitis pigmentosa. While murine Nrl loss has been characterized, studies of human NRL can identify important insights for human retinal development and disease. We utilized iPSC organoid models of retinal development to molecularly define developmental alterations in a human model of NRL loss. Consistent with the function of NRL in rod fate specification, human retinal organoids lacking NRL develop S- opsin dominant photoreceptor populations. We report generation of two distinct S-opsin expressing populations in NRL null retinal organoids and identify MEF2C as a candidate regulator of cone development. 1 Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. 2 Waisman Center, University of Wisconsin-Madison, Madison, USA. 3 Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA. -
TAS1R1 (NM 138697) Human Tagged ORF Clone Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RG219286 TAS1R1 (NM_138697) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: TAS1R1 (NM_138697) Human Tagged ORF Clone Tag: TurboGFP Symbol: TAS1R1 Synonyms: GM148; GPR70; T1R1; TR1 Vector: pCMV6-AC-GFP (PS100010) E. coli Selection: Ampicillin (100 ug/mL) Cell Selection: Neomycin This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 6 TAS1R1 (NM_138697) Human Tagged ORF Clone – RG219286 ORF Nucleotide >RG219286 representing NM_138697 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGCTGCTCTGCACGGCTCGCCTGGTCGGCCTGCAGCTTCTCATTTCCTGCTGCTGGGCCTTTGCCTGCC ATAGCACGGAGTCTTCTCCTGACTTCACCCTCCCCGGAGATTACCTCCTGGCAGGCCTGTTCCCTCTCCA TTCTGGCTGTCTGCAGGTGAGGCACAGACCCGAGGTGACCCTGTGTGACAGGTCTTGTAGCTTCAATGAG CATGGCTACCACCTCTTCCAGGCTATGCGGCTTGGGGTTGAGGAGATAAACAACTCCACGGCCCTGCTGC CCAACATCACCCTGGGGTACCAGCTGTATGATGTGTGTTCTGACTCTGCCAATGTGTATGCCACGCTGAG AGTGCTCTCCCTGCCAGGGCAACACCACATAGAGCTCCAAGGAGACCTTCTCCACTATTCCCCTACGGTG CTGGCAGTGATTGGGCCTGACAGCACCAACCGTGCTGCCACCACAGCCGCCCTGCTGAGCCCTTTCCTGG TGCCCATGATTAGCTATGCGGCCAGCAGCGAGACGCTCAGCGTGAAGCGGCAGTATCCCTCTTTCCTGCG CACCATCCCCAATGACAAGTACCAGGTGGAGACCATGGTGCTGCTGCTGCAGAAGTTCGGGTGGACCTGG -
Mismatches Between Feeding Ecology and Taste Receptor Evolution
satisfactory explanation exists (2). Furthermore, Tas1r2 is absent LETTER in all bird genomes sequenced thus far (2), irrespective of their diet. Mismatches between feeding ecology Jiang et al. (1) further contended that sea lions and dolphins and taste receptor evolution: An need not sense the umami taste because they swallow food whole. Although it is true that Tas1r1 is pseudogenized in these inconvenient truth two species, the authors ignore the previous finding that Tas1r1 is also pseudogenized or missing in all bats examined, regardless Comparative and evolutionary biology can not only verify labo- of their diet (fruits, insects, or blood) (3). Although the pseu- ratory findings of gene functions but also provide insights into dogenization of Tas1r1 in the giant panda (4) occurred at ap- their physiological roles in nature that are sometimes difficult to proximately the same time as it switched from being a meat-eater discern in the laboratory. Specifically, if our understanding of the to a plant-eater (5), and thus may be related to the feeding physiological function of a gene is complete and accurate, the ecology, herbivorous mammals, such as the horse and cow, still gene should be inactivated or pseudogenized in and only in carry an intact Tas1r1 (5). organisms in which the presumed function of the gene has be- Clearly, the presence/absence of intact Tas1r2 and Tas1r1 in come useless or harmful. On the basis of multiple independent mammals and other vertebrates is sometimes inconsistent with pseudogenizations of the sweet taste receptor gene Tas1r2 in the known functions of these genes and the involved tastes. -
Camello-XR Enables Visualization and Optogenetic Control of Gq/11 Signals and Receptor Trafficking in GPCR-Specific Domains
ARTICLE https://doi.org/10.1038/s42003-019-0292-y OPEN CaMello-XR enables visualization and optogenetic control of Gq/11 signals and receptor trafficking in GPCR-specific domains Dennis Eickelbeck1, Raziye Karapinar1, Alexander Jack 2, Sandra T. Suess1, Ruxandra Barzan3, Zohre Azimi3, 1234567890():,; Tatjana Surdin1, Michelle Grömmke1, Melanie D. Mark1, Klaus Gerwert4, Dirk Jancke3, Petra Wahle2, Katharina Spoida1 & Stefan Herlitze1 The signal specificity of G protein-coupled receptors (GPCRs) including serotonin receptors (5-HT-R) depends on the trafficking and localization of the GPCR within its subcellular signaling domain. Visualizing traffic-dependent GPCR signals in neurons is difficult, but important to understand the contribution of GPCRs to synaptic plasticity. We engineered 2+ CaMello (Ca -melanopsin-local-sensor) and CaMello-5HT2A for visualization of traffic- 2+ dependent Ca signals in 5-HT2A-R domains. These constructs consist of the light-activated 2+ Gq/11 coupled melanopsin, mCherry and GCaMP6m for visualization of Ca signals and receptor trafficking, and the 5-HT2A C-terminus for targeting into 5-HT2A-R domains. We show that the specific localization of the GPCR to its receptor domain drastically alters the dynamics and localization of the intracellular Ca2+ signals in different neuronal populations in vitro and in vivo. The CaMello method may be extended to every GPCR coupling to the Gq/ 11 pathway to help unravel new receptor-specific functions in respect to synaptic plasticity and GPCR localization. 1 Department of General Zoology and Neurobiology, ND7/31, Ruhr-University Bochum, Universitätsstr. 150, D-44780 Bochum, Germany. 2 Developmental Neurobiology, ND6/72, Ruhr-University Bochum, Universitätsstr. -
Activation Mechanism of the G Protein-Coupled Sweet Receptor Heterodimer with Sweeteners and Allosteric Agonists
Supporting Information Activation mechanism of the G protein-coupled sweet receptor heterodimer with sweeteners and allosteric agonists Soo-Kyung Kim, *† Yalu Chen, † Ravinder Abrol, †, ‡ William A. Goddard III,*† and Brian Guthrie§ †Materials and Process Simulation Center (MC 139-74), California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125; ‡Current address, Departments of Chemistry and Biochemistry, California State University, Northridge, CA 91330; §Cargill Global Food Research, 2301 Crosby Road, Wayzata, MN 55391 * CORRESPONDING AUTHOR Prof. William A. Goddard III California Institute of Technology MC 139-74, 1200 E. California Blvd., Pasadena, CA 91125; phone: 1-626-395-2731, e-mail: [email protected] Dr. Soo-Kyung Kim phone: 1-626-395-2724, e-mail: [email protected] 1 RESULTS Structures for Allosteric ligand bound at the TMD of all three TAS1Rs As described in the METHODS section, the DarwinDock procedure (1) involves sampling ~50,000 poses for each of ~10 diverse ligand conformations from which, we select finally two energetically favorable binding poses based on two scoring methods: UCav E: unified cavity energy for which we consider that interactions of the best 100 poses with the union of all residues involve in their separate binding sites (providing a uniform comparison) BE: snap binding energy considering all interactions of ligand with protein As a first validation of the predicted structures for the 7 helix TMD, we used DarwinDock to predict the binding site for the allosteric ligands to each TAS1R TMD in Table S10. Here we find, S819 [1-((1H-pyrrol-2-yl)methyl)-3-(4-isopropoxyphenyl)thiourea] is a sweet compound that interacts with the TAS1R2 TMD.(2) and Lactisole is a competitive inhibitor of the sweet taste receptor that binds to TAS1R3 TMD.(3, 4) These structures were further relaxed through annealing. -
Guthrie Cdna Resource Center
cDNA Resource Center cDNA Resource Center Catalog cDNA Resource Center Missouri University of Science and Technology 400 W 11th Rolla, MO 65409 TEL: (573) 341-7610 FAX: (573) 341-7609 EMAIL: [email protected] www.cdna.org September, 2008 1 cDNA Resource Center Visit our web site for product updates 2 cDNA Resource Center The cDNA Resource Center The cDNA Resource Center is a service provided by the faculty of the Department of Biological Sciences of Missouri University of Science and Technology. The purpose of the cDNA Resource Center is to further scientific investigation by providing cDNA clones of human proteins involved in signal transduction processes. This is achieved by providing high quality clones for important signaling proteins in a timely manner. By high quality, we mean that the clones are • Sequence verified • Propagated in a versatile vector useful in bacterial and mammalian systems • Free of extraneous 3' and 5' untranslated regions • Expression verified (in most cases) by coupled in vitro transcription/translation assays • Available in wild-type, epitope-tagged and common mutant forms (e.g., constitutively- active or dominant negative) By timely, we mean that the clones are • Usually shipped within a day from when you place your order. Clones can be ordered from our web pages, by FAX or by phone. Within the United States, clones are shipped by overnight courier (FedEx); international orders are shipped International Priority (FedEx). The clones are supplied for research purposes only. Details on use of the material are included on the Material Transfer Agreement (page 3). Clones are distributed by agreement in Invitrogen's pcDNA3.1+ vector. -
TRPV1 and Endocannabinoids: Emerging Molecular Signals That Modulate Mammalian Vision
Cells 2014, 3, 914-938; doi:10.3390/cells3030914 OPEN ACCESS cells ISSN 2073-4409 www.mdpi.com/journal/cells Review TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision 1,2,†, 1,2,† 1,† 1,2,3,4, Daniel A. Ryskamp *, Sarah Redmon , Andrew O. Jo and David Križaj * 1 Department of Ophthalmology & Visual Sciences, Moran Eye Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA; E-Mails: [email protected] (S.R.); [email protected] (A.O.J.) 2 Interdepartmental Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, UT 84132, USA 3 Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, USA 4 Center for Translational Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA † Those authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (D.A.R.); [email protected] (D.K.); Tel.: +1-801-213-2777 (D.K.); Fax: +1-801-587-8314 (D.K.). Received: 1 July 2014; in revised form: 27 August 2014 / Accepted: 5 September 2014 / Published: 12 September 2014 Abstract: Transient Receptor Potential Vanilloid 1 (TRPV1) subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the modulation of blood flow and osmoregulation but also neurotransmission, postsynaptic neuronal excitability and synaptic plasticity within the central nervous system. -
The Association of Bovine T1R Family of Receptors Polymorphisms with Cattle Growth Traits ⇑ C.L
Research in Veterinary Science xxx (2012) xxx–xxx Contents lists available at SciVerse ScienceDirect Research in Veterinary Science journal homepage: www.elsevier.com/locate/rvsc The association of bovine T1R family of receptors polymorphisms with cattle growth traits ⇑ C.L. Zhang a, J. Yuan a, Q. Wang a, Y.H. Wang a, X.T. Fang a, C.Z. Lei b, D.Y. Yang c, H. Chen a, a Institute of Cellular and Molecular Biology, Xuzhou Normal University, Xuzhou, Jiangsu, PR China b College of Animal Science and Technology, Northwest Agriculture and Forestry University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling, Shaanxi, PR China c College of Life Science, Dezhou University, Dezhou, Shandong 253023, PR China article info abstract Article history: The three members of the T1R class of taste-specific G protein-coupled receptors have been proven to Received 12 August 2011 function in combination with heterodimeric sweet and umami taste receptors in many mammals that Accepted 20 January 2012 affect food intake. This may in turn affect growth traits of livestock. We performed a comprehensive eval- Available online xxxx uation of single-nucleotide polymorphisms (SNPs) in the bovine TAS1R gene family, which encodes receptors for umami and sweet tastes. Complete DNA sequences of TAS1R1-, TAS1R2-, and TAS1R3-cod- Keywords: ing regions, obtained from 436 unrelated female cattle, representing three breeds (Qinchuan, Jiaxian Red, Taste receptors Luxi), revealed substantial coding and noncoding diversity. A total of nine SNPs in the TAS1R1 gene were SNP identified, among which seven SNPs were in the coding region, and two SNPs were in the introns. -
G Protein-Coupled Receptors
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. -
Rods Contribute to the Light-Induced Phase Shift of The
Rods contribute to the light-induced phase shift of the retinal clock in mammals Hugo Calligaro, Christine Coutanson, Raymond Najjar, Nadia Mazzaro, Howard Cooper, Nasser Haddjeri, Marie-Paule Felder-Schmittbuhl, Ouria Dkhissi-Benyahya To cite this version: Hugo Calligaro, Christine Coutanson, Raymond Najjar, Nadia Mazzaro, Howard Cooper, et al.. Rods contribute to the light-induced phase shift of the retinal clock in mammals. PLoS Biology, Public Library of Science, 2019, 17 (3), pp.e2006211. 10.1371/journal.pbio.2006211. inserm-02137592 HAL Id: inserm-02137592 https://www.hal.inserm.fr/inserm-02137592 Submitted on 23 May 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. RESEARCH ARTICLE Rods contribute to the light-induced phase shift of the retinal clock in mammals Hugo Calligaro1, Christine Coutanson1, Raymond P. Najjar2,3, Nadia Mazzaro4, Howard M. Cooper1, Nasser Haddjeri1, Marie-Paule Felder-Schmittbuhl4, Ouria Dkhissi- Benyahya1* 1 Univ Lyon, Universite Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute, Bron, France, -
Multi-Functionality of Proteins Involved in GPCR and G Protein Signaling: Making Sense of Structure–Function Continuum with In
Cellular and Molecular Life Sciences (2019) 76:4461–4492 https://doi.org/10.1007/s00018-019-03276-1 Cellular andMolecular Life Sciences REVIEW Multi‑functionality of proteins involved in GPCR and G protein signaling: making sense of structure–function continuum with intrinsic disorder‑based proteoforms Alexander V. Fonin1 · April L. Darling2 · Irina M. Kuznetsova1 · Konstantin K. Turoverov1,3 · Vladimir N. Uversky2,4 Received: 5 August 2019 / Revised: 5 August 2019 / Accepted: 12 August 2019 / Published online: 19 August 2019 © Springer Nature Switzerland AG 2019 Abstract GPCR–G protein signaling system recognizes a multitude of extracellular ligands and triggers a variety of intracellular signal- ing cascades in response. In humans, this system includes more than 800 various GPCRs and a large set of heterotrimeric G proteins. Complexity of this system goes far beyond a multitude of pair-wise ligand–GPCR and GPCR–G protein interactions. In fact, one GPCR can recognize more than one extracellular signal and interact with more than one G protein. Furthermore, one ligand can activate more than one GPCR, and multiple GPCRs can couple to the same G protein. This defnes an intricate multifunctionality of this important signaling system. Here, we show that the multifunctionality of GPCR–G protein system represents an illustrative example of the protein structure–function continuum, where structures of the involved proteins represent a complex mosaic of diferently folded regions (foldons, non-foldons, unfoldons, semi-foldons, and inducible foldons). The functionality of resulting highly dynamic conformational ensembles is fne-tuned by various post-translational modifcations and alternative splicing, and such ensembles can undergo dramatic changes at interaction with their specifc partners.