Retrograde Signaling: Understanding the Communication Between Organelles
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Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System
International Journal of Molecular Sciences Review Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System Shenglong Zou and Ujendra Kumar * Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-604-827-3660; Fax: +1-604-822-3035 Received: 9 February 2018; Accepted: 11 March 2018; Published: 13 March 2018 Abstract: The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids. Keywords: cannabinoid; endocannabinoid; receptor; signaling; central nervous system 1. Introduction The plant Cannabis sativa, better known as marijuana, has long been used for medical purpose throughout human history. -
Extracellular Adenosine Triphosphate and Adenosine in Cancer
Oncogene (2010) 29, 5346–5358 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW Extracellular adenosine triphosphate and adenosine in cancer J Stagg and MJ Smyth Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Adenosine triphosphate (ATP) is actively released in the mulated the hypothesis of purinergic neurotransmission extracellular environment in response to tissue damage (Burnstock, 1972). Burnstock’s hypothesis that ATP and cellular stress. Through the activation of P2X and could be released by cells to perform intercellular P2Y receptors, extracellular ATP enhances tissue repair, signaling was initially met with skepticism, as it seemed promotes the recruitment of immune phagocytes and unlikely that a molecule that acts as an intracellular dendritic cells, and acts as a co-activator of NLR family, source of energy would also function as an extracellular pyrin domain-containing 3 (NLRP3) inflammasomes. messenger. Nevertheless, Burnstock pursued his work The conversion of extracellular ATP to adenosine, in and, together with Che Su and John Bevan, reported contrast, essentially through the enzymatic activity of the that ATP was also released from sympathetic nerves ecto-nucleotidases CD39 and CD73, acts as a negative- during stimulation (Su et al., 1971). Three decades later, feedback mechanism to prevent excessive immune responses. following the cloning and characterization of ATP and Here we review the effects of extracellular ATP and adenosine adenosine cell surface receptors, purinergic signaling is a on tumorigenesis. First, we summarize the functions of well-established concept and constitutes an expanding extracellular ATP and adenosine in the context of tumor field of research in health and disease, including cancer immunity. -
Deciphering the Novel Role of Atmin7 in Cuticle Formation and Defense Against the Bacterial Pathogen Infection
International Journal of Molecular Sciences Article Deciphering the Novel Role of AtMIN7 in Cuticle Formation and Defense against the Bacterial Pathogen Infection Zhenzhen Zhao 1, Xianpeng Yang 2 , Shiyou Lü 3, Jiangbo Fan 4, Stephen Opiyo 1, Piao Yang 1 , Jack Mangold 1, David Mackey 5 and Ye Xia 1,* 1 Department of Plant Pathology, College of Food, Agricultural, and Environmental Science, The Ohio State University, Columbus, OH 43210, USA; [email protected] (Z.Z.); [email protected] (S.O.); [email protected] (P.Y.); [email protected] (J.M.) 2 College of Life Sciences, Shandong Normal University, Jinan 250014, China; [email protected] 3 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 434200, China; [email protected] 4 School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China; [email protected] 5 Department of Horticulture and Crop Science, College of Food, Agricultural, and Environmental Science, The Ohio State University, Columbus, OH 43210, USA; [email protected] * Correspondence: [email protected] Received: 15 July 2020; Accepted: 1 August 2020; Published: 3 August 2020 Abstract: The cuticle is the outermost layer of plant aerial tissue that interacts with the environment and protects plants against water loss and various biotic and abiotic stresses. ADP ribosylation factor guanine nucleotide exchange factor proteins (ARF-GEFs) are key components of the vesicle trafficking system. Our study discovers that AtMIN7, an Arabidopsis ARF-GEF, is critical for cuticle formation and related leaf surface defense against the bacterial pathogen Pseudomonas syringae pathovar tomato (Pto). -
Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
cancers Review Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives 1, 1, 1 2 1 Laurence Pellerin y, Lorry Carrié y , Carine Dufau , Laurence Nieto , Bruno Ségui , 1,3 1, , 1, , Thierry Levade , Joëlle Riond * z and Nathalie Andrieu-Abadie * z 1 Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, tgrCS 53717, 31037 Toulouse CEDEX 1, France; [email protected] (L.P.); [email protected] (L.C.); [email protected] (C.D.); [email protected] (B.S.); [email protected] (T.L.) 2 Institut de Pharmacologie et de Biologie Structurale, CNRS, Université Toulouse III Paul-Sabatier, UMR 5089, 205 Route de Narbonne, 31400 Toulouse, France; [email protected] 3 Laboratoire de Biochimie Métabolique, CHU Toulouse, 31059 Toulouse, France * Correspondence: [email protected] (J.R.); [email protected] (N.A.-A.); Tel.: +33-582-7416-20 (J.R.) These authors contributed equally to this work. y These authors jointly supervised this work. z Received: 15 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Simple Summary: Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. -
NGF-Dependent Retrograde Signaling: Survival Versus Death
Cell Research (2009) 19:525-526. npg © 2009 IBCB, SIBS, CAS All rights reserved 1001-0602/09 $ 30.00 RESEARCH HIGHLIGHT www.nature.com/cr NGF-dependent retrograde signaling: survival versus death Yang Zhou1, Ting-Jia Lu1, Zhi-Qi Xiong1 1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China Cell Research (2009) 19:525-526. doi: 10.1038/cr.2009.47; published online 4 May 2009 Nerve growth factor (NGF) was which could also provide as the ret- nisms underlying NGF-dependent first discovered more than 5 decades rograde signals [7]. These hypotheses retrograde signaling. Previous studies ago as a molecule that promotes the are not mutually exclusive, and mul- from Campenot’s laboratory demon- survival and maturation of develop- tiple retrograde signals may exist. strated that NGF applied to distal ax- ing neurons in the peripheral nervous In this issue, Mok and colleagues ons of sympathetic neurons supports system [1]. NGF released from target describe a fundamentally different neuronal survival without transport of cells activates tropomyosin-related retrograde mechanism in which NGF NGF towards the cell bodies or TrkA kinase A (TrkA) on axon terminals and suppresses an apoptotic signal in distal phosphorylation in the cell bodies, triggers activation of PI3K/Akt, MEK/ axons [8]. Campenot’s group devel- suggesting that NGF binding to TrkA ERK, and PLCg signaling pathways. oped compartmentalized cultures of in distal axons triggers its downstream The signal then travels retrogradely sympathetic neurons which could seg- signaling cascades locally; afterwards along axon to cell body to promote regate the distal axons from cell bod- the signals travel retrogradely to the neuronal survival [2]. -
Endocannabinoid Biosynthesis and Inactivation, from Simple to Complex
REVIEWS Drug Discovery Today Volume 15, Numbers 11/12 June 2010 Reviews POST SCREEN Endocannabinoid biosynthesis and inactivation, from simple to complex Giulio G. Muccioli Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, CHAM7230, Louvain Drug Research Institute, Universite´ catholique de Louvain, Av. E. Mounier 72, B- 1200 Bruxelles, Belgium Cannabinoid receptors, the primary molecular targets of the endocannabinoid system, are activated by specific bioactive lipids termed ‘endocannabinoids’. These lipid transmitters are synthesized from cell membrane phospholipids through multiple pathways and are inactivated by enzymatic hydrolysis, and their levels are the major parameter driving the endocannabinoid system activity. An in-depth understanding of their metabolic pathways is essential to unravel the endocannabinoid system’s role in physiological and pathological situations and to devise new therapeutic strategies based on the endocannabinoid system. Major advances both in the characterization of anandamide’s and 2- arachidonoylglycerol’s biosynthesis and inactivation pathways and in the discovery of pharmacological tools used to interfere with their metabolism have been made and are discussed in this review. Endocannabinoids are endogenous lipid transmitters that act by persistent activation or blockade and by the lack of tissue speci- binding and activating specific G-protein-coupled-receptors ficity of the ligands developed so far. A novel, more subtle, termed ‘CB1 and CB2 cannabinoid receptors’. To date, N-arachi- approach is the use of allosteric modulators, thus potentially donoylethanolamine (anandamide) and 2-arachidonoylglycerol avoiding some of the aforementioned drawbacks. However, the are the most thoroughly studied endocannabinoids. Anandamide most promising alternative strategy, now supported by a growing is a member of the N-acylethanolamine (NAE) family, a large group number of studies, is to modulate endogenous ligand levels. -
PLANT PHYSIOLOGY and ANATOMY in RELATION to HERBICIDE ACTION Physiology. James E. Hill Extension Weed Scientist As We Advance To
16 PLANT PHYSIOLOGY AND ANATOMY IN RELATION TO HERBICIDE ACTION James E. Hill Extension Weed Scientist Physiology. As we advance towards herbicides with greater selectivity and more plant toxicity, we will be reouired to know more about plant physiology and anatomy. All too often principles of plant physiology are dismissed as being too complicated to have any practical bearing on herbicide use. Yet many practices regular ly used in the field to obtain proper herbicide selectivity, have their basis of selectivity in the physiology of the plant. Plant anatomy and plant physiology will be considered together in this discussion because plant structure and function are delicately interwoven in the living plant. Plants react to herbicides within the nonnal framework of their anatomy and physiology. There are no plant processes and no structures specifically for herbicides. In fact, the lethal effects of different groups of herbicides are caused by an interference with one or more natural physiological processes in the plant. A convenient way to look at herbicides as related to plant structure and function is to divide the physiological processes into three: 1) absorption, 2) translocation, and 3) site of action. The term absorption simply means uptake, or how a chemical gets into the plant. The term translocation means movement, how a chemical moves from the place where it is absorbed to the place where it will exhibit its legal activity. Lastly, the site of action refers to the process or location where the herbicide reacts to injure or kill the plant. Each of these physiological processes are examined below in relation to herbicide selectivity, the theme of the 1976 Weed School. -
Genome-Wide Identification and Characterization of Apple P3A-Type Atpase Genes, with Implications for Alkaline Stress Responses
Article Genome-Wide Identification and Characterization of Apple P3A-Type ATPase Genes, with Implications for Alkaline Stress Responses Baiquan Ma y , Meng Gao y, Lihua Zhang, Haiyan Zhao, Lingcheng Zhu, Jing Su, Cuiying Li, Mingjun Li , Fengwang Ma * and Yangyang Yuan * State Key Laboratory of Crop Stress Biology for Arid Areas/Shaanxi Key Laboratory of Apple, College of Horticulture, Northwest A&F University, Yangling 712100, China; [email protected] (B.M.); [email protected] (M.G.); [email protected] (L.Z.); [email protected] (H.Z.); [email protected] (L.Z.); [email protected] (J.S.); [email protected] (C.L.); [email protected] (M.L.) * Correspondence: [email protected] (F.M.); [email protected] (Y.Y.); Tel.: +86-029-8708-2648 (F.M.) These authors contributed equally to this work. y Received: 4 January 2020; Accepted: 5 March 2020; Published: 6 March 2020 Abstract: The P3A-type ATPases play crucial roles in various physiological processes via the generation + of a transmembrane H gradient (DpH). However, the P3A-type ATPase superfamily in apple remains relatively uncharacterized. In this study, 15 apple P3A-type ATPase genes were identified based on the new GDDH13 draft genome sequence. The exon-intron organization of these genes, the physical and chemical properties, and conserved motifs of the encoded enzymes were investigated. Analyses of the chromosome localization and ! values of the apple P3A-type ATPase genes revealed the duplicated genes were influenced by purifying selection pressure. Six clades and frequent old duplication events were detected. Moreover, the significance of differences in the evolutionary rates of the P3A-type ATPase genes were revealed. -
Metabotropic Glutamate Receptors: Intracellular Signaling Pathways Urs Gerber1, Christine E Gee1,2 and Pascal Benquet3
Metabotropic glutamate receptors: intracellular signaling pathways Urs Gerber1, Christine E Gee1,2 and Pascal Benquet3 Metabotropic glutamate receptors are classified into three mGluRs, will not be discussed explicitly here as this groups, primarily on the basis of sequence similarity and topic is the subject of several comprehensive recent whether they positively couple to the phospholipase C cascade reviews (e.g. see [5]). or negatively couple to adenylyl cyclases. The past decade of research, drawing on sophisticated molecular approaches, has Transduction within the mGluR revealed a multitude of additional intracellular components that Upon binding of glutamate, a conformational change in assemble as protein scaffolds around neuronal metabotropic homodimeric mGluRs promotes the coupling of G pro- glutamate receptors, establishing functional links to teins to specific intracellular domains. Structural studies, postsynaptic density structures, to membrane-bound enzymes beginning with the crystallization and characterization of and ion channels, and to the nucleus. Characterization of these the agonist-bound and ‘unliganded’ forms of the gluta- novel transduction mechanisms is providing new insights into mate binding site of mGluR1, provided initial insights the roles of metabotropic glutamate receptors in the regulation into the underlying process [6]. Agonist binding stabilizes and modulation of diverse functions in the nervous system. the closed conformation of the extracellular domain and Addresses results in G protein activation that is dependent upon a 1 Brain Research Institute, University of Zurich, CH-8057 Zurich, disulfide bridge between conserved cysteine residues in Switzerland the extracellular agonist binding loop and the third trans- 2 Novartis Institutes for Biomedical Research, Novartis Pharma AG, membrane domain [6,7]. -
Neurotransmission: Emerging Roles of Endocannabinoids
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Dispatch R549 and Keller, L. (2005). Clonal reproduction (2001). Genetic variation in a host- sexes reveals ontogenetic conflict in by males and females in the little fire ant. parasite association: potential for Drosophila. Evolution Int. J. Org. Nature 435, 1230-1234. coevolution and frequency-dependent Evolution 98, 1671–1675. 5. Hamilton, W.D., Axelrod, R., and Tanese, selection. Evolution Int. J. Org. Evolution R. (1990). Sexual reproduction as an 55, 1136–1145. adaptation to resist parasites (A Review). 8. Liersch, S., and Schmid-Hempel, P. Institute of Evolutionary Biology, Proc. Natl. Acad. Sci. USA 87, (1998). Genetic variation within social University of Edinburgh, West Mains 3566–3573. insect colonies reduces parasite load. Road, Edinburgh EH9 3JT, UK. 6. Kondrashov, A.S. (1982). Selection Proc. R. Soc. Lond. B. Biol. Sci. 265, against harmful mutations in large sexual 221–225. E-mail: [email protected] and asexual populations. Genet. Res. 40, 9. Chippendale, A.K., Gibson, J.R., and 325–332. Rice, W.R. (2001). Negative genetic 7. Carius, H.J., Little, T.J., and Ebert, D. correlation for adult fitness between DOI: 10.1016/j.cub.2005.07.001 Neurotransmission: Emerging requires a sustained (5–10 minute) activation of presynaptic CB1 Roles of Endocannabinoids receptors [12,13]. Modulation of synaptic transmission by endocannabinoids Postsynaptic release of endocannabinoids can inhibit presynaptic was initially studied using non- neurotransmitter release on short and long timescales. This retrograde physiological methods, such as inhibition occurs at both excitatory and inhibitory synapses and may seconds-long depolarization or provide a mechanism for synaptic gain control, short-term associative application of high-affinity plasticity, reduction of synaptic crosstalk, and metaplasticity. -
Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives
Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation de Andrade Mello, Paola, Robson Coutinho-Silva, and Luiz Eduardo Baggio Savio. 2017. “Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives.” Frontiers in Immunology 8 (1): 1526. doi:10.3389/fimmu.2017.01526. http://dx.doi.org/10.3389/ fimmu.2017.01526. Published Version doi:10.3389/fimmu.2017.01526 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493041 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA REVIEW published: 14 November 2017 doi: 10.3389/fimmu.2017.01526 Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives Paola de Andrade Mello1, Robson Coutinho-Silva 2* and Luiz Eduardo Baggio Savio2* 1 Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Cancer is still one of the world’s most pressing health-care challenges, leading to a high number of deaths worldwide. Immunotherapy is a new developing therapy that Edited by: boosts patient’s immune system to fight cancer by modifying tumor–immune cells Salem Chouaib, interaction in the tumor microenvironment (TME). -
Cell Signaling and Regulation of Metabolism Objectives
Cell Signaling and Regulation of Metabolism Objectives By the end of this lecture, students are expected to: • Differentiate different steps in signaling pathways • Describe the second messenger systems • Recognize the function of signaling pathways for • Signal transmission • Amplification • Discuss the role of signaling pathways in regulation and integration of metabolism No cell lives in isolation • Cells communicate with each other • Cells send and receive information (signals) • Information is relayed within cell to produce a response Signaling Process • Recognition of signal – Receptors • Transduction – Change of external signal into intracellular message with amplification and formation of second messenger • Effect – Modification of cell metabolism and function General Signaling Pathway Signaling Cascades Recognition • Performed by receptors • Ligand will produce response only in cells that have receptors for this particular ligand • Each cell has a specific set of receptors Different Responses to the Same Signaling Molecule. (A) Different Cells Different Responses to the Same Signaling Molecule. (B) One Cell but, Different Pathways Hypoglycemia Glucagon secretion Hepatocyte: Glucagon/receptor binding Second messenger: cAMP Response: Enzyme phosphorylation P P Glycogen synthase Glycogen phosphorylase (Inactive form) (Active form) Inhibition of glycogenesis Stimulation of glycogenolysis GTP-Dependant Regulatory Proteins (G-Proteins) G-Proteins: Trimeric membrane proteins (αβγ) G-stimulatory (Gs) and G-inhibitory (Gi) binds to GTP/GDP