DOCSLIB.ORG

Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals Amy Desaulniers University of Nebraska-Lincoln, [email protected]

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals Amy Desaulniers University of Nebraska-Lincoln, Amy.Desaulniers@Huskers.Unl.Edu University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Faculty Papers and Publications in Animal Science Animal Science Department 12-10-2017 Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals Amy Desaulniers University of Nebraska-Lincoln, [email protected] Rebecca A. Cederberg University of Nebraska-Lincoln, [email protected] Clay A. Lents USDA, ARS, USMARC, [email protected] Brett R. White University of Nebraska-Lincoln, [email protected] Follow this and additional works at: http://digitalcommons.unl.edu/animalscifacpub Part of the Genetics and Genomics Commons, and the Meat Science Commons Desaulniers, Amy; Cederberg, Rebecca A.; Lents, Clay A.; and White, Brett R., "Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals" (2017). Faculty Papers and Publications in Animal Science. 986. http://digitalcommons.unl.edu/animalscifacpub/986 This Article is brought to you for free and open access by the Animal Science Department at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Faculty Papers and Publications in Animal Science by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. REVIEW published: 11 December 2017 doi: 10.3389/fendo.2017.00269 Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals Amy T. Desaulniers1, Rebecca A. Cederberg1, Clay A. Lents 2 and Brett R. White1* 1 Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States, 2 USDA, ARS, USMARC, Clay Center, NE, United States Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, signifying high selection pressure and a critical biological role. However, the GnRH2 gene is absent (e.g., rat) or inactivated (e.g., cow and sheep) in some species but retained in others (e.g., human, horse, and pig). Likewise, many species (e.g., human, chimpanzee, cow, and sheep) retain the GnRHR2 gene but lack the appropriate coding sequence Edited by: to produce a full-length protein due to gene coding errors; although production of Ivana Bjelobaba, University of Belgrade, Serbia GnRHR2 in humans remains controversial. Certain mammals lack the GnRHR2 gene Reviewed by: (e.g., mouse) or most exons entirely (e.g., rat). In contrast, old world monkeys, musk Emilie Rissman, shrews, and pigs maintain the coding sequence required to produce a functional North Carolina State University, GnRHR2. Like GnRHR1, GnRHR2 is a 7-transmembrane, G protein-coupled receptor United States Buffy Sue Ellsworth, that interacts with Gαq/11 to mediate cell signaling. However, GnRHR2 retains a cytoplas- Southern Illinois University mic tail and is only 40% homologous to GnRHR1. A role for GnRH2 and its receptor Carbondale, United States in mammals has been elusive, likely because common laboratory models lack both the *Correspondence: ligand and receptor. Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; Brett R. White [email protected] transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from Specialty section: GnRH1/GnRHR1. Indeed, GnRH2 and its receptor are not physiological modulators This article was submitted to Neuroendocrine Science, of gonadotropin secretion in mammals. Instead, GnRH2 and GnRHR2 coordinate the a section of the journal interaction between nutritional status and sexual behavior in the female brain. Within Frontiers in Endocrinology peripheral tissues, GnRH2 and its receptor are novel regulators of reproductive organs. Received: 08 July 2017 GnRH2 and GnRHR2 directly stimulate steroidogenesis within the porcine testis. Accepted: 26 September 2017 Published: 11 December 2017 In the female, GnRH2 and its receptor may help mediate placental function, implanta- Citation: tion, and ovarian steroidogenesis. Furthermore, both the GnRH2 and GnRHR2 genes Desaulniers AT, Cederberg RA, are expressed in human reproductive tumors and represent emerging targets for can- Lents CA and White BR (2017) Expression and Role of cer treatment. Thus, GnRH2 and GnRHR2 have diverse functions in mammals which Gonadotropin-Releasing Hormone 2 remain largely unexplored. and Its Receptor in Mammals. Front. Endocrinol. 8:269. Keywords: GnRH2, GnRH2 receptor, reproductive function, G protein-coupled receptor, G protein-coupled doi: 10.3389/fendo.2017.00269 receptor signal transduction, autocrine/paracrine mechanisms, testis, cancer Frontiers in Endocrinology | www.frontiersin.org 1 December 2017 | Volume 8 | Article 269 Desaulniers et al. GnRH2 and GnRHR2 in Mammals BACKGROUND ancient form of GnRH (18). In contrast, GnRH1 evolved 350 million years ago and its sequence varies greatly among verte- The Classical Form of Mammalian brates (19). Gonadotropin-Releasing Hormone The Gene for GnRH2 (GnRH1) GnRH2 is not merely a splice variant of the GnRH1 gene; instead, The classical, hypophysiotropic GnRH1 is hailed as the master it is produced from its own gene that encodes the peptide, prepro- regulator of reproduction in mammals. GnRH1 is a decapeptide GnRH2 (20). TheGnRH2 gene is located on chromosome 20 in (pGlu–His–Trp–Ser–Tyr–Gly–Leu–Arg–Pro–Gly–NH2) humans, chimpanzees, and orangutans, chromosome 13 in the produced by hypothalamic neurons and secreted in a pulsatile cow, chromosome 22 in the horse, chromosome 10 in the rhesus manner into hypophyseal portal capillaries where it travels to macaque, and chromosome 17 in the pig (21). The genomic orienta- the anterior pituitary gland. GnRH1 then binds to its receptor tion of the GnRH2 gene is highly conserved across species (21, 22). (GnRHR1) on gonadotrope cells, promoting the synthesis and It is flanked by the PTPRA and MRPS26 genes in all mammalian secretion of the gonadotropins, follicle-stimulating hormone and non-mammalian vertebrates examined to date (21, 22). The (FSH) and luteinizing hormone (LH), into peripheral circulation PTPRA gene resides about 5–6 kb upstream of the GnRH2 gene where they act on their target organs, the gonads. In females, FSH (21) and encodes the enzyme, receptor-type tyrosine-protein stimulates follicular development, whereas LH promotes ovula- phosphatase α, which is critical for neural development (23). The tion and maintenance of the corpus luteum. Within the testes, MRPS26 gene resides about 300 bp downstream of the GnRH2 FSH regulates spermatogenesis and LH elicits secretion of testos- gene (21), encoding mitochondrial ribosome protein S26, which terone. Ultimately, the gonads cease to function and reproduction assists in protein synthesis (24). A graphical representation of the is halted in the absence of GnRH1 (1–3). porcine GnRH2 gene is depicted in Figure 1A. GnRH Variants in Mammals The human GnRH2 gene has three coding exons like the GnRH1 gene; however, the GnRH2 gene is notably shorter Gonadotropin-releasing hormone 1 was first identified in the (2.1 versus 5.1 kb), primarily due to differences in intron length hypothalami of pigs and sheep (4–6) and was originally thought (20). Otherwise, organization of the GnRH1 and GnRH2 genes to be a novel peptide. However, 23 other forms of GnRH have remain similar (25). The first coding exon in humans encodes the since been discovered (7), all with 10 amino acids and at least signal sequence, mature decapeptide, and a portion of the GnRH- a 50% sequence identity (8). Within these forms, the sequences associated peptide (GAP). The second and third exons encode of both the N-terminus (pGlu–His–Trp–Ser) and C-terminus the remaining GAP (20). Likewise, porcine prepro-GnRH2 (Pro–Gly–NH2) are conserved (7, 9). The amino acid substitu- is encoded by 3 exons and yields a 110 amino acid product tions only occur between residues 5 and 8 (7, 9). In vertebrates, (Figure 1B) that must undergo post-translational proteolytic three forms of GnRH (GnRH1, GnRH2, and GnRH3) are the processing for functionality (20). most common. The third form of GnRH (GnRH3; pGlu–His– Trp–Ser–His–Asp–Trp–Lys–Pro–Gly–NH2) was first discovered Presence of the GnRH2 Gene in Mammals in lamprey (10) but the GnRH3 gene has only been confirmed in Although the GnRH2 gene was first identified in humans fish and amphibians to date (7, 11). Therefore, only GnRH1 and (20), Stewart et al. (21) examined the genomes of mammals GnRH2 are produced in mammals (7). encompassing 10 orders for the presence of the GnRH2 gene. GONADOTROPIN-RELEASING The GnRH2 gene was positively identified in 21 animals. Using bioinformatics, the authors concluded that gene coding errors HORMONE 2 likely prevent the successful production of GnRH2 in many species (21). A summary of the coding errors present in the The Second Form of Mammalian GnRH GnRH2 gene of mammals is available in Table 1. A premature (GnRH2) stop codon truncates the mature decapeptide in the chimpanzee, A second structural variant of GnRH, GnRH2, has been identi- orangutan, mouse lemur, sheep, and cat (21, 26), whereas the fied in mammals. Like GnRH1, GnRH2 is a decapeptide but it rabbit, pika, cow, dog, cat, and dolphin GnRH2 genes encode was first isolated from the hypothalami of 10,000 chickens and an inactive peptide (21, 26). Early evidence implied that the rat therefore named “chicken GnRH2” (12). It was later discovered and mouse also maintain a GnRH2 gene as immunoreactive in mammals, the first being marsupials (13), and renamed simply GnRH2 was detected in the rodent brain (27–29). Although it “GnRH2” to prevent confusion (14). Since then, GnRH2 has was later determined that the mouse genome only maintains a been found in animals of every vertebrate class including primi- fragment of the GnRH2 gene (exon 1) on chromosome 2 and it tive orders (e.g., bony fish) as well as complex mammals 15( ). is completely deleted from chromosome 3 in the rat (21, 22, 30).
Load more

Recommended publications
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • The Adapted Ears of Big Cats and Golden Moles: Exotic Outcomes of the Evolutionary Radiation of Mammals
    FEATURED ARTICLE The Adapted Ears of Big Cats and Golden Moles: Exotic Outcomes of the Evolutionary Radiation of Mammals Edward J. Walsh and JoAnn McGee Through the process of natural selection, diverse organs and organ systems abound throughout the animal kingdom. In light of such abundant and assorted diversity, evolutionary adaptations have spawned a host of peculiar physiologies. The anatomical oddities that underlie these physiologies and behaviors are the telltale indicators of trait specialization. Following from this, the purpose of this article is to consider a number of auditory “inventions” brought about through natural selection in two phylogenetically distinct groups of mammals, the largely fossorial golden moles (Order Afrosoricida, Family Chrysochloridae) and the carnivorous felids of the genus Panthera along with its taxonomic neigh- bor, the clouded leopard (Neofelis nebulosa). In the Beginning The first vertebrate land invasion occurred during the Early Carboniferous period some 370 million years ago. The primitive but essential scaffolding of what would become the middle and inner ears of mammals was present at this time, although the evolution of the osseous (bony) middle ear system and the optimization of cochlear fea- tures and function would play out over the following 100 million years. Through natural selection, the evolution of the middle ear system, composed of three small articu- lated bones, the malleus, incus, and stapes, and a highly structured and coiled inner ear, came to represent all marsupial and placental (therian) mammals on the planet Figure 1. Schematics of the outer, middle, and inner ears (A) and thus far studied. The consequences of this evolution were the organ of Corti in cross section (B) of a placental mammal.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • Subterranean Mammals Show Convergent Regression in Ocular Genes and Enhancers, Along with Adaptation to Tunneling
    RESEARCH ARTICLE Subterranean mammals show convergent regression in ocular genes and enhancers, along with adaptation to tunneling Raghavendran Partha1, Bharesh K Chauhan2,3, Zelia Ferreira1, Joseph D Robinson4, Kira Lathrop2,3, Ken K Nischal2,3, Maria Chikina1*, Nathan L Clark1* 1Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States; 2UPMC Eye Center, Children’s Hospital of Pittsburgh, Pittsburgh, United States; 3Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, United States; 4Department of Molecular and Cell Biology, University of California, Berkeley, United States Abstract The underground environment imposes unique demands on life that have led subterranean species to evolve specialized traits, many of which evolved convergently. We studied convergence in evolutionary rate in subterranean mammals in order to associate phenotypic evolution with specific genetic regions. We identified a strong excess of vision- and skin-related genes that changed at accelerated rates in the subterranean environment due to relaxed constraint and adaptive evolution. We also demonstrate that ocular-specific transcriptional enhancers were convergently accelerated, whereas enhancers active outside the eye were not. Furthermore, several uncharacterized genes and regulatory sequences demonstrated convergence and thus constitute novel candidate sequences for congenital ocular disorders. The strong evidence of convergence in these species indicates that evolution in this environment is recurrent and predictable and can be used to gain insights into phenotype–genotype relationships. DOI: https://doi.org/10.7554/eLife.25884.001 *For correspondence: [email protected] (MC); [email protected] (NLC) Competing interests: The Introduction authors declare that no The subterranean habitat has been colonized by numerous animal species for its shelter and unique competing interests exist.
    [Show full text]
  • 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.
    [Show full text]
  • Food Deprivation Explains Effects of Mouthbrooding on Ovaries and Steroid Hormones, but Not Brain Neuropeptide and Receptor Mrnas, in an African Cichlid fish
    Hormones and Behavior 62 (2012) 18–26 Contents lists available at SciVerse ScienceDirect Hormones and Behavior journal homepage: www.elsevier.com/locate/yhbeh Food deprivation explains effects of mouthbrooding on ovaries and steroid hormones, but not brain neuropeptide and receptor mRNAs, in an African cichlid fish Brian P. Grone ⁎,1, Russ E. Carpenter, Malinda Lee, Karen P. Maruska, Russell D. Fernald Biology Department, Stanford University, Stanford, CA 94305‐5020, USA article info abstract Article history: Feeding behavior and reproduction are coordinately regulated by the brain via neurotransmitters, circulating Received 19 December 2011 hormones, and neuropeptides. Reduced feeding allows animals to engage in other behaviors important for Revised 10 April 2012 fitness, including mating and parental care. Some fishes cease feeding for weeks at a time in order to provide Accepted 15 April 2012 care to their young by brooding them inside the male or female parent's mouth. Maternal mouthbrooding is Available online 26 April 2012 known to impact circulating hormones and subsequent reproductive cycles, but neither the full effects of food deprivation nor the neural mechanisms are known. Here we ask what effects mouthbrooding has on Keywords: Feeding several physiological processes including gonad and body mass, brain neuropeptide and receptor gene ex- Reproduction pression, and circulating steroid hormones in a mouthbrooding cichlid species, Astatotilapia burtoni.We Parental care ask whether any observed changes can be explained by food deprivation, and show that during mouthbrood- Teleost ing, ovary size and circulating levels of androgens and estrogens match those seen during food deprivation. Cichlid Levels of gonadotropin-releasing hormone 1 (GnRH1) mRNA in the brain were low in food-deprived females Testosterone compared to controls and in mouthbrooding females compared to gravid females.
    [Show full text]
  • G Protein‐Coupled Receptors
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors Stephen PH Alexander1 , Arthur Christopoulos2 , Anthony P Davenport3 , Eamonn Kelly4, Alistair Mathie5 , John A Peters6 , Emma L Veale5 ,JaneFArmstrong7 , Elena Faccenda7 ,SimonDHarding7 ,AdamJPawson7 , Joanna L Sharman7 , Christopher Southan7 , Jamie A Davies7 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia 3Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK 4School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 5Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 6Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 7Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website.
    [Show full text]
  • Supplementary Table 1
    Supplementary Table 1. 492 genes are unique to 0 h post-heat timepoint. The name, p-value, fold change, location and family of each gene are indicated. Genes were filtered for an absolute value log2 ration 1.5 and a significance value of p ≤ 0.05. Symbol p-value Log Gene Name Location Family Ratio ABCA13 1.87E-02 3.292 ATP-binding cassette, sub-family unknown transporter A (ABC1), member 13 ABCB1 1.93E-02 −1.819 ATP-binding cassette, sub-family Plasma transporter B (MDR/TAP), member 1 Membrane ABCC3 2.83E-02 2.016 ATP-binding cassette, sub-family Plasma transporter C (CFTR/MRP), member 3 Membrane ABHD6 7.79E-03 −2.717 abhydrolase domain containing 6 Cytoplasm enzyme ACAT1 4.10E-02 3.009 acetyl-CoA acetyltransferase 1 Cytoplasm enzyme ACBD4 2.66E-03 1.722 acyl-CoA binding domain unknown other containing 4 ACSL5 1.86E-02 −2.876 acyl-CoA synthetase long-chain Cytoplasm enzyme family member 5 ADAM23 3.33E-02 −3.008 ADAM metallopeptidase domain Plasma peptidase 23 Membrane ADAM29 5.58E-03 3.463 ADAM metallopeptidase domain Plasma peptidase 29 Membrane ADAMTS17 2.67E-04 3.051 ADAM metallopeptidase with Extracellular other thrombospondin type 1 motif, 17 Space ADCYAP1R1 1.20E-02 1.848 adenylate cyclase activating Plasma G-protein polypeptide 1 (pituitary) receptor Membrane coupled type I receptor ADH6 (includes 4.02E-02 −1.845 alcohol dehydrogenase 6 (class Cytoplasm enzyme EG:130) V) AHSA2 1.54E-04 −1.6 AHA1, activator of heat shock unknown other 90kDa protein ATPase homolog 2 (yeast) AK5 3.32E-02 1.658 adenylate kinase 5 Cytoplasm kinase AK7
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2003/0106074 A1 Serafini (43) Pub
    US 2003O106074A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0106074 A1 Serafini (43) Pub. Date: Jun. 5, 2003 (54) COLLECTIONS OF TRANSGENIC ANIMAL Publication Classification LINES (LIVING LIBRARY) (51) Int. Cl." ...................... A01K 67/033; AO1K 67/027 (76) Inventor: Tito Andrew Serafini, San Mateo, CA (52) U.S. Cl. ................................................... 800/8: 800/14 (US) (57) ABSTRACT Correspondence Address: The invention provides collections of transgenic animals and PENNIE AND EDMONDS vectors for producing transgenic animals, which transgenic 1155 AVENUE OF THE AMERICAS animals and vectors have a transgene comprising Sequences NEW YORK, NY 100362711 encoding a detectable or Selectable marker, the expression of which marker is under the control of regulatory Sequences (21) Appl. No.: 10/077,025 from an endogenous gene Such that when the transgene is present in the genome of the transgenic animal, the detect (22) Filed: Feb. 14, 2002 able or Selectable marker has the same expression pattern as the endogenous gene. Such transgenic animals can then be Related U.S. Application Data used to detect, isolate and/or Select pure populations of cells having a particular functional characteristic. The isolated (63) Continuation-in-part of application No. 09/783,487, cells have uses in gene discovery, target identification and filed on Feb. 14, 2001. validation, genomic and proteomic analysis, etc. Patent Application Publication Jun. 5, 2003. Sheet 1 of 13 US 2003/0106074 A1 sixxx; : ?,graecaeaeaeaeae ·:>`()~(ºrº?anaeru: !!¿*(:,!!!!!(!!!!!..”):straes) - k wis **** ************ FIG . 1 A FIG. 1B Patent Application Publication Jun. 5, 2003. Sheet 2 of 13 US 2003/0106074 A1 clone2 *********** ******$$x***** *******.
    [Show full text]
  • Loss of RXFP2 and INSL3 Genes in Afrotheria Shows That Testicular Descent Is the Ancestral Condition in Placental Mammals
    SHORT REPORTS Loss of RXFP2 and INSL3 genes in Afrotheria shows that testicular descent is the ancestral condition in placental mammals Virag Sharma1,2,3, Thomas Lehmann4, Heiko Stuckas5, Liane Funke1, Michael Hiller1,2,3* 1 Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, 2 Max Planck Institute for the Physics of Complex Systems, Dresden, Germany, 3 Center for Systems Biology Dresden, Germany, 4 Senckenberg Research Institute and Natural History Museum Frankfurt, Frankfurt am Main, Germany, 5 Museum of Zoology, Senckenberg Dresden, Germany a1111111111 a1111111111 * [email protected] a1111111111 a1111111111 a1111111111 Abstract Descent of testes from a position near the kidneys into the lower abdomen or into the scro- tum is an important developmental process that occurs in all placental mammals, with the OPEN ACCESS exception of five afrotherian lineages. Since soft-tissue structures like testes are not pre- Citation: Sharma V, Lehmann T, Stuckas H, Funke served in the fossil record and since key parts of the placental mammal phylogeny remain L, Hiller M (2018) Loss of RXFP2 and INSL3 genes controversial, it has been debated whether testicular descent is the ancestral or derived con- in Afrotheria shows that testicular descent is the dition in placental mammals. To resolve this debate, we used genomic data of 71 mamma- ancestral condition in placental mammals. PLoS lian species and analyzed the evolution of two key genes (relaxin/insulin-like family peptide Biol 16(6): e2005293. https://doi.org/10.1371/ journal.pbio.2005293 receptor 2 [RXFP2] and insulin-like 3 [INSL3]) that induce the development of the guberna- culum, the ligament that is crucial for testicular descent.
    [Show full text]
  • The DNA Sequence and Comparative Analysis of Human Chromosome 20
    articles The DNA sequence and comparative analysis of human chromosome 20 P. Deloukas, L. H. Matthews, J. Ashurst, J. Burton, J. G. R. Gilbert, M. Jones, G. Stavrides, J. P. Almeida, A. K. Babbage, C. L. Bagguley, J. Bailey, K. F. Barlow, K. N. Bates, L. M. Beard, D. M. Beare, O. P. Beasley, C. P. Bird, S. E. Blakey, A. M. Bridgeman, A. J. Brown, D. Buck, W. Burrill, A. P. Butler, C. Carder, N. P. Carter, J. C. Chapman, M. Clamp, G. Clark, L. N. Clark, S. Y. Clark, C. M. Clee, S. Clegg, V. E. Cobley, R. E. Collier, R. Connor, N. R. Corby, A. Coulson, G. J. Coville, R. Deadman, P. Dhami, M. Dunn, A. G. Ellington, J. A. Frankland, A. Fraser, L. French, P. Garner, D. V. Grafham, C. Grif®ths, M. N. D. Grif®ths, R. Gwilliam, R. E. Hall, S. Hammond, J. L. Harley, P. D. Heath, S. Ho, J. L. Holden, P. J. Howden, E. Huckle, A. R. Hunt, S. E. Hunt, K. Jekosch, C. M. Johnson, D. Johnson, M. P. Kay, A. M. Kimberley, A. King, A. Knights, G. K. Laird, S. Lawlor, M. H. Lehvaslaiho, M. Leversha, C. Lloyd, D. M. Lloyd, J. D. Lovell, V. L. Marsh, S. L. Martin, L. J. McConnachie, K. McLay, A. A. McMurray, S. Milne, D. Mistry, M. J. F. Moore, J. C. Mullikin, T. Nickerson, K. Oliver, A. Parker, R. Patel, T. A. V. Pearce, A. I. Peck, B. J. C. T. Phillimore, S. R. Prathalingam, R. W. Plumb, H. Ramsay, C. M.
    [Show full text]