Oligomerization of the Human Adenosine A2a Receptor Is Driven by 2 the Intrinsically Disordered C-Terminus
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Peropsin, a Novel Visual Pigment-Like Protein Located in the Apical Microvilli of the Retinal Pigment Epithelium
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 9893–9898, September 1997 Neurobiology Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium HUI SUN*, DEBRA J. GILBERT†,NEAL G. COPELAND†,NANCY A. JENKINS†, AND JEREMY NATHANS*‡§¶i *Department of Molecular Biology and Genetics, §Department of Neuroscience, ¶Department of Ophthalmology, ‡Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and †Mammalian Genetics Laboratory, Advanced BioScience Laboratories Basic Research Program, National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, MD 21702 Contributed by Jeremy Nathans, June 19, 1997 ABSTRACT A visual pigment-like protein, referred to as bovine RPE binds to all-trans but not 11-cis retinal and absorbs peropsin, has been identified by large-scale sequencing of both visible and ultraviolet light (8, 9). The sequences of cDNAs derived from human ocular tissues. The corresponding retinochrome and RGR opsin form a distinct and highly mRNA was found only in the eye, where it is localized to the divergent branch within the visual pigment family (6, 10). retinal pigment epithelium (RPE). Peropsin immunoreactiv- Whether retinochrome and RGR act as signal-transducing ity, visualized by light and electron microscopy, localizes the light receptors, participate in the visual cycle as retinal isomer- protein to the apical face of the RPE, and most prominently ases, or function in both capacities, is not known. to the microvilli that surround the photoreceptor outer seg- In the vertebrate eye, the RPE lies adjacent to the photo- ments. These observations suggest that peropsin may play a receptor cells and performs a number of functions critical for role in RPE physiology either by detecting light directly or by the viability and activity of the retina (11). -
P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells
fphar-09-00149 February 26, 2018 Time: 17:57 # 1 ORIGINAL RESEARCH published: 28 February 2018 doi: 10.3389/fphar.2018.00149 P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells Mabrouka Salem1,2, Alain Tremblay2, Julie Pelletier2, Bernard Robaye3 and Jean Sévigny1,2* 1 Département de Microbiologie-Infectiologie et d’Immunologie, Faculté de Médecine, Université Laval, Québec City, QC, Canada, 2 Centre de Recherche du CHU de Québec – Université Laval, Québec City, QC, Canada, 3 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP- 2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 Edited by: ligand UDP induced expression and secretion of CXCL10. For the other studies, we Kenneth A. Jacobson, −=− National Institutes of Health (NIH), took advantage of mice deficient in P2Y6 (P2ry6 ). Similar expression levels of P2Y1, −=− United States P2Y2, P2X2, P2X4, and A2A were detected in P2ry6 and WT IEC. Agonists of Reviewed by: TLR3 (poly(I:C)), TLR4 (LPS), P2Y1, and P2Y2 increased the expression and secretion Fernando Ochoa-Cortes, of CXCL10 more prominently in P2ry6−=− IEC than in WT IEC. CXCL10 expression Universidad Autónoma de San Luis −=− Potosí, Mexico and secretion induced by poly(I:C) in both P2ry6 and WT IEC were inhibited by Markus Neurath, general P2 antagonists (suramin and Reactive-Blue-2), by apyrase, and by specific Universitätsklinikum Erlangen, Germany antagonists of P2Y1, P2Y2, P2Y6 (only in WT), and P2X4. -
Immunosuppression Via Adenosine Receptor Activation by Adenosine
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Crossref RESEARCH ARTICLE elifesciences.org Immunosuppression via adenosine receptor activation by adenosine monophosphate released from apoptotic cells Hiroshi Yamaguchi1, Toshihiko Maruyama2, Yoshihiro Urade2†, Shigekazu Nagata1,3* 1Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan; 3Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kyoto, Japan Abstract Apoptosis is coupled with recruitment of macrophages for engulfment of dead cells, and with compensatory proliferation of neighboring cells. Yet, this death process is silent, and it does not cause inflammation. The molecular mechanisms underlying anti-inflammatory nature of the apoptotic process remains poorly understood. In this study, we found that the culture supernatant of apoptotic cells activated the macrophages to express anti-inflammatory genes such as Nr4a and Thbs1. A high level of AMP accumulated in the apoptotic cell supernatant in a Pannexin1-dependent manner. A nucleotidase inhibitor and A2a adenosine receptor antagonist inhibited the apoptotic *For correspondence: snagata@ supernatant-induced gene expression, suggesting AMP was metabolized to adenosine by an mfour.med.kyoto-u.ac.jp ecto-5’-nucleotidase expressed on macrophages, to activate the macrophage A2a adenosine receptor. Intraperitoneal injection of zymosan into Adora2a- or Panx1-deficient mice produced † Present address: Molecular high, sustained levels of inflammatory mediators in the peritoneal lavage. These results indicated Sleep Biology Laboratory, that AMP from apoptotic cells suppresses inflammation as a ‘calm down’ signal. WPI-International Institute for DOI: 10.7554/eLife.02172.001 Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan Competing interests: The Introduction authors declare that no competing interests exist. -
Constitutive Activation of G Protein-Coupled Receptors and Diseases: Insights Into Mechanisms of Activation and Therapeutics
Pharmacology & Therapeutics 120 (2008) 129–148 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Associate editor: S. Enna Constitutive activation of G protein-coupled receptors and diseases: Insights into mechanisms of activation and therapeutics Ya-Xiong Tao ⁎ Department of Anatomy, Physiology and Pharmacology, 212 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA article info abstract The existence of constitutive activity for G protein-coupled receptors (GPCRs) was first described in 1980s. In Keywords: 1991, the first naturally occurring constitutively active mutations in GPCRs that cause diseases were reported G protein-coupled receptor Disease in rhodopsin. Since then, numerous constitutively active mutations that cause human diseases were reported Constitutively active mutation in several additional receptors. More recently, loss of constitutive activity was postulated to also cause Inverse agonist diseases. Animal models expressing some of these mutants confirmed the roles of these mutations in the Mechanism of activation pathogenesis of the diseases. Detailed functional studies of these naturally occurring mutations, combined Transgenic model with homology modeling using rhodopsin crystal structure as the template, lead to important insights into the mechanism of activation in the absence of crystal structure of GPCRs in active state. Search for inverse Abbreviations: agonists on these receptors will be critical for correcting the diseases cause by activating mutations in GPCRs. ADRP, autosomal dominant retinitis pigmentosa Theoretically, these inverse agonists are better therapeutics than neutral antagonists in treating genetic AgRP, Agouti-related protein AR, adrenergic receptor diseases caused by constitutively activating mutations in GPCRs. CAM, constitutively active mutant © 2008 Elsevier Inc. -
Dimers of Serotonin Receptors: Impact on Ligand Affinity and Signaling
Dimers of serotonin receptors: impact on ligand affinity and signaling Luc Maroteaux, Catherine Béchade, Anne Roumier To cite this version: Luc Maroteaux, Catherine Béchade, Anne Roumier. Dimers of serotonin receptors: impact on ligand affinity and signaling. Biochimie, Elsevier, 2019, 161, pp.23-33. 10.1016/j.biochi.2019.01.009. hal- 01996206 HAL Id: hal-01996206 https://hal.archives-ouvertes.fr/hal-01996206 Submitted on 28 Jan 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. Maroteaux et al., 1 Dimers of serotonin receptors: impact on ligand affinity and signaling. Luc Maroteaux1,2,3, Catherine Béchade1,2,3, and Anne Roumier1,2,3 Affiliations: 1: INSERM UMR-S839, S1270, Paris, 75005, France; 2Sorbonne Université, Paris, 75005, France; 3Institut du Fer à Moulin, Paris, 75005, France. Running title: Dimers of serotonin receptors Correspondence should be addressed to: Luc Maroteaux INSERM UMR-S839, S1270, 17 rue du Fer a Moulin Paris, 75005, France; E-mail : [email protected] Abstract Membrane receptors often form complexes with other membrane proteins that directly interact with different effectors of the signal transduction machinery. G-protein-coupled receptors (GPCRs) were for long time considered as single pharmacological entities. -
The Interaction of Selective A1 and A2A Adenosine Receptor Antagonists with Magnesium and Zinc Ions in Mice: Behavioural, Biochemical and Molecular Studies
International Journal of Molecular Sciences Article The Interaction of Selective A1 and A2A Adenosine Receptor Antagonists with Magnesium and Zinc Ions in Mice: Behavioural, Biochemical and Molecular Studies Aleksandra Szopa 1,* , Karolina Bogatko 1, Mariola Herbet 2 , Anna Serefko 1 , Marta Ostrowska 2 , Sylwia Wo´sko 1, Katarzyna Swi´ ˛ader 3, Bernadeta Szewczyk 4, Aleksandra Wla´z 5, Piotr Skałecki 6, Andrzej Wróbel 7 , Sławomir Mandziuk 8, Aleksandra Pochodyła 3, Anna Kudela 2, Jarosław Dudka 2, Maria Radziwo ´n-Zaleska 9, Piotr Wla´z 10 and Ewa Poleszak 1,* 1 Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, 1 Chod´zkiStreet, PL 20–093 Lublin, Poland; [email protected] (K.B.); [email protected] (A.S.); [email protected] (S.W.) 2 Chair and Department of Toxicology, Medical University of Lublin, 8 Chod´zkiStreet, PL 20–093 Lublin, Poland; [email protected] (M.H.); [email protected] (M.O.); [email protected] (A.K.) [email protected] (J.D.) 3 Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chod´zkiStreet, PL 20–093 Lublin, Poland; [email protected] (K.S.);´ [email protected] (A.P.) 4 Department of Neurobiology, Polish Academy of Sciences, Maj Institute of Pharmacology, 12 Sm˛etnaStreet, PL 31–343 Kraków, Poland; [email protected] 5 Department of Pathophysiology, Medical University of Lublin, 8 Jaczewskiego Street, PL 20–090 Lublin, Poland; [email protected] Citation: Szopa, A.; Bogatko, K.; 6 Department of Commodity Science and Processing of Raw Animal Materials, University of Life Sciences, Herbet, M.; Serefko, A.; Ostrowska, 13 Akademicka Street, PL 20–950 Lublin, Poland; [email protected] M.; Wo´sko,S.; Swi´ ˛ader, K.; Szewczyk, 7 Second Department of Gynecology, 8 Jaczewskiego Street, PL 20–090 Lublin, Poland; B.; Wla´z,A.; Skałecki, P.; et al. -
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, -
G Protein-Coupled Receptor Heteromers Are Key Players in Substance Use Disorder
G protein-coupled receptor heteromers are key players in substance use disorder. Lyes Derouiche, Dominique Massotte To cite this version: Lyes Derouiche, Dominique Massotte. G protein-coupled receptor heteromers are key players in substance use disorder.. Neuroscience & Biobehavioral Reviews, Oxford: Elsevier Ltd., 2019, 106, 10.1016/j.neubiorev.2018.09.026. hal-02264889 HAL Id: hal-02264889 https://hal.archives-ouvertes.fr/hal-02264889 Submitted on 18 Mar 2020 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. G Protein-Coupled Receptor Heteromers Are Key Players in Substance Use Disorder. Lyes Derouiche and Dominique Massotte* Institut des Neurosciences Cellulaires et Integratives, UPR 3212 5 rue Blaise Pascal, F-67000 Strasbourg, France Highlights Heteromers are functional entities with behavioral impact Heteromers are increasingly recognized as key players in substance use disorder Heteromers may be part of larger functional multiprotein complexes Heteromers represent emerging innovative therapeutic targets Funding sources: The work was received the financial support of the Fondation pour la Recherche Médicale (DPA20140129364), the CNRS and the University of Strasbourg. L. Derouiche was the recipient of an IDEX post-doctoral fellowship of the University of Strasbourg. * Author for correspondence : Dominique Massotte, INCI UPR 3212, 5 rue Blaise Pascal, F-67000 Strasbourg, France, email: [email protected] 1 Abstract G protein–coupled receptors (GPCR) represent the largest family of membrane proteins in the human genome. -
Melanopsin: an Opsin in Melanophores, Brain, and Eye
Proc. Natl. Acad. Sci. USA Vol. 95, pp. 340–345, January 1998 Neurobiology Melanopsin: An opsin in melanophores, brain, and eye IGNACIO PROVENCIO*, GUISEN JIANG*, WILLEM J. DE GRIP†,WILLIAM PA¨R HAYES‡, AND MARK D. ROLLAG*§ *Department of Anatomy and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; †Institute of Cellular Signaling, University of Nijmegen, 6500 HB Nijmegen, The Netherlands; and ‡Department of Biology, The Catholic University of America, Washington, DC 20064 Edited by Jeremy Nathans, Johns Hopkins University School of Medicine, Baltimore, MD, and approved November 5, 1997 (received for review September 16, 1997) ABSTRACT We have identified an opsin, melanopsin, in supernatants subjected to SDSyPAGE analysis and subse- photosensitive dermal melanophores of Xenopus laevis. Its quent electroblotting onto a poly(vinylidene difluoride) mem- deduced amino acid sequence shares greatest homology with brane. The blot was probed with a 1:2,000 dilution of antisera cephalopod opsins. The predicted secondary structure of (CERN 886) raised against bovine rhodopsin and detected by melanopsin indicates the presence of a long cytoplasmic tail enhanced chemiluminescence. with multiple putative phosphorylation sites, suggesting that cDNA Library Screen. A X. laevis dermal melanophore this opsin’s function may be finely regulated. Melanopsin oligo(dT) cDNA library was screened with a mixture of mRNA is expressed in hypothalamic sites thought to contain 32P-labeled probes. Probes were synthesized by random prim- deep brain photoreceptors and in the iris, a structure known ing of TA-cloned (Invitrogen) fragments of X. laevis rhodopsin to be directly photosensitive in amphibians. Melanopsin mes- (7) (759 bp) and violet opsin (8) (279 bp) cDNAs. -
Homology Model of the Human 5–HT1A Receptor Using the Crystal Structure of Bovine Rhodopsin Urmila J
CODEN IEJMAT Internet Electronic Journal of Molecular Design 2006, 5, 403–415 ISSN 1538–6414 BioChem Press http://www.biochempress.com Internet Electronic Journal of Molecular Design July 2006, Volume 5, Number 7, Pages 403–415 Editor: Ovidiu Ivanciuc Special issue dedicated to Professor Lemont B. Kier on the occasion of the 75th birthday Homology Model of the Human 5–HT1A Receptor Using the Crystal Structure of Bovine Rhodopsin Urmila J. Joshi, Falgun H. Shah, and Sonali H. Tikhele Department of Pharmaceutical Chemistry, Prin. K. M. Kundnani College of Pharmacy, Cuffe Parade, Colaba, Mumbai–400005 Received: December 28, 2005; Revised: June 2, 2006; Accepted: July 8, 2006; Published: July 31, 2006 Citation of the article: U. J. Joshi, F. H. Shah, and S. H. Tikhele, Homology Model of the Human 5–HT1A Receptor Using the Crystal Structure of Bovine Rhodopsin, Internet Electron. J. Mol. Des. 2006, 5, 403– 415, http://www.biochempress.com. Copyright © 2006 BioChem Press U. J. Joshi, F. H. Shah, and S. H. Tikhele Internet Electronic Journal of Molecular Design 2006, 5, 403–415 Internet Electronic Journal BioChem Press of Molecular Design http://www.biochempress.com Homology Model of the Human 5–HT1A Receptor Using the Crystal Structure of Bovine Rhodopsin # Urmila J. Joshi,* Falgun H. Shah, and Sonali H. Tikhele Department of Pharmaceutical Chemistry, Prin. K. M. Kundnani College of Pharmacy, Cuffe Parade, Colaba, Mumbai–400005 Received: December 28, 2005; Revised: June 2, 2006; Accepted: July 8, 2006; Published: July 31, 2006 Internet Electron. J. Mol. Des. 2006, 5 (7), 403–415 Abstract Motivation. The 5–HT1A receptor, a member of class A GPCRs, is associated with psychiatric disorders like depression and anxiety, thus representing an important target for developing new drugs. -
REVIEW Dimerization and Oligomerization of G-Protein
435 REVIEW Dimerization and oligomerization of G-protein-coupled receptors: debated structures with established and emerging functions La´szlo´ Szidonya1, Miklo´s Cserzo˝ 1 and La´szlo´ Hunyady1,2 1Department of Physiology, Semmelweis University, PO Box 259, H-1444 Budapest, Hungary 2Laboratory for Neurobiochemistry and Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, H-1444 Budapest, Hungary (Correspondence should be addressed to L Hunyady; Email: [email protected]) Abstract Dimerization or oligomerization of G-protein-coupled homo- or heterodimeric or oligomeric complexes, in which receptors (GPCRs) is a novel concept, which may lead to receptor monomers have stable direct interactions. However, the reevaluation of the actions of pharmacological ligands, overwhelming amounts of data suggest that many GPCRs hormones, neurotransmitters, and other mediators acting on exhibit functional properties that require direct or indirect GPCRs. Although a large number of data obtained using interactions between clustered receptors. Although it is different biophysical, biochemical and structural methods, difficult to conclude, about the exact nature of these and functional approaches argue for dimerization or interactions, dimerization or oligomerization of GPCRs is a oligomerization of these receptors, several publications useful paradigm for pharmacologists to study properties of criticized the applied methods and challenged the concept. receptors, which require functionally important clustering of The aim of this paper is to review the data that support the receptors, such as trafficking of newly synthesized receptors to concept of receptor oligomerization, and the most important the cell surface, allosteric modulation of ligand binding, arguments against it. We conclude that it will require major signaling specificity, co-internalization, or cross-inhibition of methodical improvements to obtain decisive proof, whether GPCRs. -
Cell Surface Targeting of -␦ Opioid Receptor Heterodimers by RTP4
Cell surface targeting of -␦ opioid receptor heterodimers by RTP4 Fabien M. De´ caillot, Raphael Rozenfeld, Achla Gupta, and Lakshmi A. Devi* Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029 Edited by Susan G. Amara, University of Pittsburgh School of Medicine, Pittsburgh, PA, and approved August 22, 2008 (received for review April 29, 2008) opioid receptors are G protein–coupled receptors that mediate heterodimers, respectively. These findings, together with the the pain-relieving effects of clinically used analgesics, such as observation that the development of tolerance correlates with morphine. Accumulating evidence shows that -␦ opioid het- the enhanced surface expression (through externalization) of ␦ erodimers have a pharmacologic profile distinct from those of the receptors in dorsal root ganglion neurons expressing receptors or ␦ homodimers. Because the heterodimers exhibit distinct (15), support the idea that mechanisms and/or proteins that signaling properties, the protein and mechanism regulating their modulate the level of -␦ complexes serve as critical factors in levels have significant effects on morphine-mediated physiology. the development of tolerance (16). Thus, the factors influencing We report the characterization of RTP4, a Golgi chaperone, as a the homodimer-to-heterodimer ratio become a key issue in regulator of the levels of heterodimers at the cell surface. We show determining the net effect of an opiate. Moreover, they could that the association with RTP4 protects -␦ receptors from ubiq- redirect the coupling of opioid receptors to a distinct signal uitination and degradation. This leads to increases in surface transduction pathway (17, 18). But very little is known about the heterodimer levels, thereby affecting signaling.