DOCSLIB.ORG

The Mitochondrion

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Mitochondrion The mitochondrion: the powerhouse behind Professor Elizabeth Jonas neurotransmission ‘We think we have found a key molecule that forms a major cell death-inducing mitochondrial ion channel’ THE MITOCHONDRION: THE POWERHOUSE BEHIND NEUROTRANSMISSION Professor Elizabeth Jonas and her colleagues at Yale University study the function of cell components called Ca2+ Ca2+ Ca2+ mitochondria and their role in neurotransmission. In particular, Professor Jonas is interested in characterising how 3. Calcium is released from mitochondria. 2. Repeated action potentials (tetanus) invade When another action potential invades 1. An1. action An action potential potential invades inv adesthe terminal. the 2. Repeated action potentials 3. Calcium is released from channels in the mitochondrial membrane affect neuronal function during processes like memory formation and terminal. the terminal, the increased calcium levels Someterminal. vesicles fuse, releasing (tetanus) invade terminal. mitochondria. learning, and how they enhance or reduce neuronal viability during disease. Many vesicles fuse. from mitochondrial release plus plasma neurotransmitter.Some vesicles fuse, releasing Many vesicles fuse. When another action potential neurotransmitter. CalciumCalcium is ta isk takenen up up into into mitochondria. invadesmembrane the terminal, Ca2+ influx increase vesicle mitochondria. the fusion,increased potentiating calcium levelsneurotransmission. from mitochondrial release plus plasma membrane Ca2+ influx Neurotransmission – firing on all can have profound effects on neuronal but they participate in carefully regulating increase vesicle fusion, cylinders. function and viability, and implications in calcium levels during neurotransmission. and calcium dynamics of neurotransmission the mitochondrial permeability transition potentiatingand its classical neurotr roleansmission. is to prevent other disease. This process also has important effects on and on studying how these interact, like pore. The channel can open and close, members of the Bcl-2 family from initiating Neurons form an incredibly complex ATP production by the mitochondria and filling in pieces of a jigsaw puzzle. In fact, allowing mitochondrial contents to travel a cell death program known as apoptosis. network throughout our bodies, and play The nuts and bolts of neurotransmission: can affect how excitable the neuron is. If Professor Jonas is credited with developing through it. Exposure to high concentrations However, Professor Jonas’ team has a fundamental physiological role. Neurons the mitochondrial system. the calcium-regulating or ATP-producing a completely new technique to study ion of calcium results in permeability transition found that Bcl-xL can also improve the form the link between brain and body by processes become altered this can change channels inside living cells, using two pore opening which may act physiologically efficiency of mitochondrial function during transmitting information to and from the Much of the energy demands of the excitability of a neuron over time, or can electrodes, whereby one electrode is in the neuron to help re-release sequestered neurotransmission by interacting with the brain and spinal cord to peripheral tissues neurotransmission are met by a small even cause the death of the neuron. In fact, sheathed inside another and is used to calcium, but, if open for a longer time, ATP synthase enzyme and the mitochondrial such as our muscles. The brain can encode organelle present in neurons called the channels in mitochondria are important probe for ion channels in the membranes of may also disrupt mitochondrial function. permeability transition pore. Jonas’ team information as patterns of neural impulses mitochondrion. Mitochondria are membrane- factors in cell death and may contribute organelles, like mitochondria. Interestingly, These events ultimately lead to loss of finds that Bcl-xL essentially contributes to that pass from neuron to neuron. Neurons bound structures which produce a substance substantially to the permanent alteration in her initial goal when applying this technique normal neurotransmission and neuronal prevention of leaking of H+ ions through also comprise the brain and spinal tissue called adenosine triphosphate (ATP), which neuronal function in the brain that underlies was to find ion channels on the membranes death. In addition, the team is interested the mitochondrial permeability transition itself and normal neuronal function forms the is used by the neuron as a source of energy learning and memory formation and other of large secretory granules in invertebrate in other molecules that can interact with, pore, which improves the ability of the basis for a diverse set of processes including during neurotransmission. Mitochondrial forms of neural plasticity. These processes neurons. She was surprised when instead, and affect the behaviour of mitochondrial mitochondria to increase ATP production, thought, memory formation and movement. efficiency refers to how much ATP is may go very wrong in neurodegenerative she discovered calcium release channels in pores or otherwise modulate mitochondrial while reducing the metabolic demands on Neurotransmission is the procedure by which produced per molecule of glucose or oxygen diseases like Alzheimer’s or Parkinson’s mitochondria, a discovery which sparked activity and neurotransmission. The Bcl-2 mitochondria. These processes may partially neuronal cells communicate with each other. taken up by a cell or organism, and when this disease; therefore, mitochondrial dysfunction her intense interest in mitochondrial family of proteins, originally identified in underlie the potential of Bcl-xL to protect Typically, neurons do not directly touch each process is inefficient less ATP is produced. is heavily implicated in these diseases. channels and the role they play in disease. cancer cells, is involved in the regulation neurons from degeneration and may also other, but rather exchange information at Neurotransmission also involves the uptake Understanding what substances pass in and of mitochondrial membrane permeability play a role in memory formation in the brain. specialised structures surrounding a very of calcium through small channels or How is this process regulated? out of the mitochondrion, when they move among other processes. Several members of thin gap between neurons called a synapse. pores in the neuronal membrane. Calcium in and out, and what molecules permit or the family tend to promote cell death, while Synaptic plasticity At a synapse, an activated neuron, through facilitates the release of neurotransmitters Professor Elizabeth Jonas and her team are block their movement and why, are key others prevent cell death. This comprises a which a neural impulse has travelled, will from the neuron. However, once interested in the regulation of ion transport elements of Professor Jonas’ research. For particularly important function for cancer So how do these complex phenomena release molecules called neurotransmitters neurotransmission is complete, the calcium across the mitochondrial membrane, with example, the team discovered that a segment cells, which rely on anti-death Bcl-2 family on a small scale in neurons relate to which can travel across the synaptic cleft and that entered the neuron needs to be cleared, a view to understanding the role of the of an enzyme called ATP synthase, which members to promote their cancer-inducing appreciable effects in human beings? One bind to receptors in a second neuron. In this to allow the system to reset. Mitochondria mitochondrion in normal activities such as is involved in the production of ATP in the behaviour. In neurons the anti-death Bcl-2 mechanism these factors can affect is manner, the neural impulse can propagate play a role in helping to mop up this calcium learning and memory, as well as its role in mitochondrion, functions as a channel in the family members prevent death due to many synaptic plasticity, which is the tendency of a along the second neuron and continue on its through an intricate system of channels in disease processes which result in abnormal inner mitochondrial membrane, where it is forms of injury or aging, and this function synapse to become stronger or weaker over way. As you might have guessed, this process their membranes. They also re-release the neuronal activity or neuronal cell death. embedded. Professor Jonas believes that in in neurons is termed neuroprotection. time, as a result of changes in its activity. requires energy, and alterations in the sequestered calcium and so not only do they The team focuses on identifying the most this discovery, the team has uncovered the One member of the family is called Bcl-xL. It is hypothesised that this process could mechanism by which this energy is provided help to reset calcium levels in the neuron, important molecular players in the energy identity of a very important channel, called Bcl-xL spans the mitochondrial membrane underlie our ability to create memories and WWW.SCIENTIAPUBLICATIONS.COM WWW.SCIENTIAPUBLICATIONS.COM PROFESSOR ELIZABETH JONAS Professor Jonas and her team have hypothesised that neuroprotective molecules like Bcl-xL may prevent the onset of neurodegenerative disease through their interactions with mitochondrial ion channels. While pro-apoptotic Bcl-xL appears to contribute to neuronal cell death processes in diseases like stroke, full length Bcl-xL may promote neuronal survival under non-ischemic conditions. In fact, Professor Jonas
Load more

Recommended publications
  • The First Cells Were Most Likely Very Simple Prokaryotic Forms. Ra- Spirochetes
    T HE O RIGIN OF E UKARYOTIC C ELLS The first cells were most likely very simple prokaryotic forms. Ra- spirochetes. Ingestion of prokaryotes that resembled present-day diometric dating indicates that the earth is 4 to 5 billion years old cyanobacteria could have led to the endosymbiotic development of and that prokaryotes may have arisen more than 3.5 billion years chloroplasts in plants. ago. Eukaryotes are thought to have first appeared about 1.5 billion Another hypothesis for the evolution of eukaryotic cells proposes years ago. that the prokaryotic cell membrane invaginated (folded inward) to en- The eukaryotic cell might have evolved when a large anaerobic close copies of its genetic material (figure 1b). This invagination re- (living without oxygen) amoeboid prokaryote ingested small aerobic (liv- sulted in the formation of several double-membrane-bound entities ing with oxygen) bacteria and stabilized them instead of digesting them. (organelles) in a single cell. These entities could then have evolved This idea is known as the endosymbiont hypothesis (figure 1a) and into the eukaryotic mitochondrion, nucleus, and chloroplasts. was first proposed by Lynn Margulis, a biologist at Boston Univer- Although the exact mechanism for the evolution of the eu- sity. (Symbiosis is an intimate association between two organisms karyotic cell will never be known with certainty, the emergence of of different species.) According to this hypothesis, the aerobic bac- the eukaryotic cell led to a dramatic increase in the complexity and teria developed into mitochondria, which are the sites of aerobic diversity of life-forms on the earth. At first, these newly formed eu- respiration and most energy conversion in eukaryotic cells.
    [Show full text]
  • Bioenergetics and Metabolism Mitochondria Chloroplasts
    Bioenergetics and metabolism Mitochondria Chloroplasts Peroxisomes B. Balen Chemiosmosis common pathway of mitochondria, chloroplasts and prokaryotes to harness energy for biological purposes → chemiosmotic coupling – ATP synthesis (chemi) + membrane transport (osmosis) Prokaryotes – plasma membrane → ATP production Eukaryotes – plasma membrane → transport processes – membranes of cell compartments – energy-converting organelles → production of ATP • Mitochondria – fungi, animals, plants • Plastids (chloroplasts) – plants The essential requirements for chemiosmosis source of high-energy e- membrane with embedded proton pump and ATP synthase energy from sunlight or the pump harnesses the energy of e- transfer to pump H+→ oxidation of foodstuffs is proton gradient across the membrane used to create H+ gradient + across a membrane H gradient serves as an energy store that can be used to drive ATP synthesis Figures 14-1; 14-2 Molecular Biology of the Cell (© Garland Science 2008) Electron transport processes (A) mitochondrion converts energy from chemical fuels (B) chloroplast converts energy from sunlight → electron-motive force generated by the 2 photosystems enables the chloroplast to drive electron transfer from H2O to carbohydrate → chloroplast electron transfer is opposite of electron transfer in a mitochondrion Figure 14-3 Molecular Biology of the Cell (© Garland Science 2008) Carbohydrate molecules and O2 are products of the chloroplast and inputs for the mitochondrion Figure 2-41; 2-76 Molecular Biology of the Cell (© Garland
    [Show full text]
  • Molecular Biology of Neuronal Voltage-Gated Calcium Channels
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 30, No 3, 123-130, September 1998 Molecular biology of neuronal voltage-gated calcium channels Hemin Chin and is capable of directing expression of calcium channel activity in heterologous expression systems. In the central Genetics Research Branch, Division of Basic and Clinical Neuroscience Research, nervous system (CNS), VGCCs are expressed by five National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, distinct a1 subunit genes (α1A, α1B, α1C, α1D and α1E), U.S.A. which exhibit further variations due to alternative splicing of the primary RNA transcripts. The α1C and, α1D su b u n i t Accepted 3 August 1998 genes encode dihydropyridine (DHP)-sensitive L-type channels, while the three other α1 subunit genes (α1A, α1B and α1E) give rise to DHP-insensitive P/Q-, N- and R-type channels, respectively. The α2 and δ s u b u n i t proteins are produced by proteolytic cleavage of a larger precursor produced by the single α2-δ gene (Table 1). Introduction Three alternatively spliced variants of the α2 subunit are expressed in a tissue-specific manner. Two variants Calcium ions are important intracellular messengers have been isolated from the brain and skeletal muscle mediating a number of neuronal functions including neuro- (Kim et al., 1992; Williams et al., 1992), and a distinct transmitter release, neurosecretion, neuronal excitation, third splice variant which is expressed in glial cells has survival of eurons, and regulation of gene expression. been recently identified (Puro et al., 1996). In addition to The entry of calcium across the plasmamembrane in the gene encoding the skeletal muscle β subunit, three response to membrane depolarization or activation of 1 other β subunit genes (β2, β3 and β4) have been isolated neurotransmitter receptors represents a major pathway thus far.
    [Show full text]
  • Origin and Evolution of Plastids and Mitochondria : the Phylogenetic Diversity of Algae
    Cah. Biol. Mar. (2001) 42 : 11-24 Origin and evolution of plastids and mitochondria : the phylogenetic diversity of algae Catherine BOYEN*, Marie-Pierre OUDOT and Susan LOISEAUX-DE GOER UMR 1931 CNRS-Goëmar, Station Biologique CNRS-INSU-Université Paris 6, Place Georges-Teissier, BP 74, F29682 Roscoff Cedex, France. *corresponding author Fax: 33 2 98 29 23 24 ; E-mail: [email protected] Abstract: This review presents an account of the current knowledge concerning the endosymbiotic origin of plastids and mitochondria. The importance of algae as providing a large reservoir of diversified evolutionary models is emphasized. Several reviews describing the plastidial and mitochondrial genome organization and gene content have been published recently. Therefore we provide a survey of the different approaches that are used to investigate the evolution of organellar genomes since the endosymbiotic events. The importance of integrating population genetics concepts to understand better the global evolution of the cytoplasmically inherited organelles is especially emphasized. Résumé : Cette revue fait le point des connaissances actuelles concernant l’origine endosymbiotique des plastes et des mito- chondries en insistant plus particulièrement sur les données portant sur les algues. Ces organismes représentent en effet des lignées eucaryotiques indépendantes très diverses, et constituent ainsi un abondant réservoir de modèles évolutifs. L’organisation et le contenu en gènes des génomes plastidiaux et mitochondriaux chez les eucaryotes ont été détaillés exhaustivement dans plusieurs revues récentes. Nous présentons donc une synthèse des différentes approches utilisées pour comprendre l’évolution de ces génomes organitiques depuis l’événement endosymbiotique. En particulier nous soulignons l’importance des concepts de la génétique des populations pour mieux comprendre l’évolution des génomes à transmission cytoplasmique dans la cellule eucaryote.
    [Show full text]
  • Chemical Neurotransmission
    Cambridge University Press 978-1-107-02598-1 — Stahl's Essential Psychopharmacology 4th Edition Excerpt More Information Chapter1 Chemical neurotransmission Anatomical versus chemical basis of Beyond the second messenger to a neurotransmission 1 phosphoprotein cascade triggering gene 16 Principles of chemical neurotransmission 5 expression Neurotransmitters 5 How neurotransmission triggers gene 18 Neurotransmission: classic, retrograde, expression 18 and volume 6 Molecular mechanism of gene expression Excitation–secretion coupling 8 Epigenetics 24 Signal transduction cascades 9 What are the molecular mechanisms 24 Overview 9 of epigenetics? Forming a second messenger 11 How epigenetics maintains or changes the status quo 26 Beyond the second messenger to phosphoprotein messengers 13 Summary 26 Modern psychopharmacology is largely the story of neurons, not unlike millions of telephone wires chemical neurotransmission. To understand the actions within thousands upon thousands of cables. The ana- of drugs on the brain, to grasp the impact of diseases tomically addressed brain is thus a complex wiring upon the central nervous system, and to interpret the diagram, ferrying electrical impulses to wherever behavioral consequences of psychiatric medicines, the “wire” is plugged in (i.e., at a synapse). Synapses one must be fluent in the language and principles of canformonmanypartsofaneuron,notjustthe chemical neurotransmission. The importance of this dendrites as axodendritic synapses, but also on the fact cannot be overstated for the student of psychophar- soma as axosomatic synapses, and even at the begin- macology. This chapter forms the foundation for the ning and at the end of axons (axoaxonic synapses) entire book, and the roadmap for one’s journey through (Figure 1-2).
    [Show full text]
  • Localization of the Mitochondrial Ftsz Protein in a Dividing Mitochondrion Mitochondria Are Ubiquitous Organelles That Play Crit
    C2001 The Japan Mendel Society Cytologia 66: 421-425, 2001 Localization of the Mitochondrial FtsZ Protein in a Dividing Mitochondrion Manabu Takahara*, Haruko Kuroiwa, Shin-ya Miyagishima, Toshiyuki Mori and Tsuneyoshi Kuroiwa Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan Accepted November 2, 2001 Summary FtsZ protein is essential for bacterial cell division, and is also involved in plastid and mitochondrial division. However, little is known of the function of FtsZ in the mitochondrial division process. Here, using electron microscopy, we revealed that the mitochondrial FtsZ (CmFtsZ 1) local- izes at the constricted isthmus of a dividing mitochondrion on the inner (matrix-side) surface of the mitochondrion. These results strongly suggest that the mitochondrial FtsZ acts as a ring structure on the inner surface of mitochondria. Key words Cyanidionschyzon merolae, FtsZ, FtsZ ring, mitochondria, mitochondrion-dividing ring (MD ring) . Mitochondria are ubiquitous organelles that play critical roles in respiration and ATP synthesis in almost all eukaryotic cells. Mitochondria are thought to have originated from a-proteobacteria through an endosymbiont event. Like bacteria, they multiply by the binary fission of pre-existing mitochondria. Although the role of mitochondria in respiration and ATP production is well under- stood, little is known about the proliferation of mitochondria in cells. In plastids, which also arose from prokaryotic endosymbionts, the ring structure that appears at the constricted isthmus of a dividing plastid (the plastid-dividing ring or PD ring) has been iden- tified as the plastid division apparatus (Mita et al. 1986). The PD ring is widespread among plants and algae, and consists of an outer (cytosolic) ring and an inner (stromal) ring in most species.
    [Show full text]
  • A True Symbiosis for the Mitochondria Evolution
    : O tics pe ge n r A e c n c e e o s i s B Morelli et al, Bioenergetics 2016, 5:2 Bioenergetics: Open Access DOI: 10.4172/2167-7662.1000137 ISSN: 2167-7662 Letter to Editor Open Access A True Symbiosis for the Mitochondria Evolution Alessandro Morelli1* and Camillo Rosano2 1University of Genova, School of Medical and Pharmaceutical Sciences, Department of Pharmacy, Biochemistry Laboratory, Italy 2UO Proteomics, IRCCS AOU San Martino, IST National Institute for Cancer Research, Largo Rosanna Benzi, Genova, Italy *Corresponding author: Alessandro Morelli, University of Genova, School of Medical and Pharmaceutical Sciences, Department of Pharmacy, Biochemistry Laboratory, Italy, Tel: +39 010 3538153; E-mail: [email protected] Rec Date: June 10, 2016; Acc Date: June 22, 2016; Pub Date: June 24, 2016 Copyright: © 2016 Morelli A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation: Morelli A, Rosano C (2016) A True Symbiosis for the Mitochondria Evolution. Bioenergetics 5: 228. doi:10.4172/2167-7662.1000137 Introduction assimilated within eukaryotic cells much later than what initially thought [10]. Endosymbiotic theory (or Symbiogenesis) is an evolutionary theory that was initially proposed more than 100 years ago [1] to explain the These revolutionary data together with the hypothesis by our and origins of eukaryotic cells from the prokaryotic ones. This theory others groups about the possible existence of “extra-mitochondrial” postulated that several key organelles of eukaryotes could have been structures in Eukaryotes with OXPHOS and ATP synthesis perfectly originated as a symbiosis between separate organisms.
    [Show full text]
  • Part III: Modeling Neurotransmission – a Cholinergic Synapse
    Part III: Modeling Neurotransmission – A Cholinergic Synapse Operation of the nervous system is dependent on the flow of information through chains of neurons functionally connected by synapses. The neuron conducting impulses toward the synapse is the presynaptic neuron, and the neuron transmitting the signal away from the synapse is the postsynaptic neuron. Chemical synapses are specialized for release and reception of chemical neurotransmitters. For the most part, neurotransmitter receptors in the membrane of the postsynaptic cell are either 1.) channel-linked receptors, which mediate fast synaptic transmission, or 2.) G protein-linked receptors, which oversee slow synaptic responses. Channel-linked receptors are ligand-gated ion channels that interact directly with a neurotransmitter and are called ionotropic receptors. Alternatively, metabotropic receptors do not have a channel that opens or closes but rather, are linked to a G-protein. Once the neurotransmitter binds to the metabotropic receptor, the receptor activates the G-protein which, in turn, goes on to activate another molecule. 3a. Model the ionotropic cholinergic synapse shown below. Be sure to label all of the following: voltage-gated sodium channel, voltage-gated potassium channel, neurotransmitter, synaptic vesicle, presynaptic cell, postsynaptic cell, potassium leak channel, sodium-potassium pump, synaptic cleft, acetylcholine receptor, acetylcholinesterase, calcium channel. When a nerve impulse (action potential) reaches the axon terminal, it sets into motion a chain of events that triggers the release of neurotransmitter. You will next model the events of neurotransmission at a cholinergic synapse. Cholinergic synapses utilize acetylcholine as the chemical of neurotransmission. MSOE Center for BioMolecular Modeling Synapse Kit: Section 3-6 | 1 Step 1 - Action potential arrives at the Step 2 - Calcium channels open in the terminal end of the presynaptic cell.
    [Show full text]
  • Virus World As an Evolutionary Network of Viruses and Capsidless Selfish Elements
    Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements Koonin, E. V., & Dolja, V. V. (2014). Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements. Microbiology and Molecular Biology Reviews, 78(2), 278-303. doi:10.1128/MMBR.00049-13 10.1128/MMBR.00049-13 American Society for Microbiology Version of Record http://cdss.library.oregonstate.edu/sa-termsofuse Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements Eugene V. Koonin,a Valerian V. Doljab National Center for Biotechnology Information, National Library of Medicine, Bethesda, Maryland, USAa; Department of Botany and Plant Pathology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon, USAb Downloaded from SUMMARY ..................................................................................................................................................278 INTRODUCTION ............................................................................................................................................278 PREVALENCE OF REPLICATION SYSTEM COMPONENTS COMPARED TO CAPSID PROTEINS AMONG VIRUS HALLMARK GENES.......................279 CLASSIFICATION OF VIRUSES BY REPLICATION-EXPRESSION STRATEGY: TYPICAL VIRUSES AND CAPSIDLESS FORMS ................................279 EVOLUTIONARY RELATIONSHIPS BETWEEN VIRUSES AND CAPSIDLESS VIRUS-LIKE GENETIC ELEMENTS ..............................................280 Capsidless Derivatives of Positive-Strand RNA Viruses....................................................................................................280
    [Show full text]
  • Regulation of Neuronal Communication by G Protein-Coupled Receptors ⇑ Yunhong Huang, Amantha Thathiah
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 589 (2015) 1607–1619 journal homepage: www.FEBSLetters.org Review Regulation of neuronal communication by G protein-coupled receptors ⇑ Yunhong Huang, Amantha Thathiah VIB Center for the Biology of Disease, Leuven, Belgium Center for Human Genetics (CME) and Leuven Institute for Neurodegenerative Diseases (LIND), University of Leuven (KUL), Leuven, Belgium article info abstract Article history: Neuronal communication plays an essential role in the propagation of information in the brain and Received 31 March 2015 requires a precisely orchestrated connectivity between neurons. Synaptic transmission is the mech- Revised 5 May 2015 anism through which neurons communicate with each other. It is a strictly regulated process which Accepted 5 May 2015 involves membrane depolarization, the cellular exocytosis machinery, neurotransmitter release Available online 14 May 2015 from synaptic vesicles into the synaptic cleft, and the interaction between ion channels, G Edited by Wilhelm Just protein-coupled receptors (GPCRs), and downstream effector molecules. The focus of this review is to explore the role of GPCRs and G protein-signaling in neurotransmission, to highlight the func- tion of GPCRs, which are localized in both presynaptic and postsynaptic membrane terminals, in reg- Keywords: G protein-coupled receptors ulation of intrasynaptic and intersynaptic communication, and to discuss the involvement of G-proteins astrocytic GPCRs in the regulation of neuronal communication. Neuronal communication Ó 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Synaptic transmission Signaling Astrocytes Neurons Autoreceptors Neurotransmitters 1.
    [Show full text]
  • RIM-BP2 Primes Synaptic Vesicles Via Recruitment of Munc13-1 At
    RESEARCH ARTICLE RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses Marisa M Brockmann1†, Marta Maglione2,3,4†, Claudia G Willmes5†, Alexander Stumpf6, Boris A Bouazza1, Laura M Velasquez6, M Katharina Grauel1, Prateep Beed6, Martin Lehmann3, Niclas Gimber6, Jan Schmoranzer4, Stephan J Sigrist2,4,5*, Christian Rosenmund1,4*, Dietmar Schmitz4,5,6* 1Institut fu¨ r Neurophysiologie, Charite´ – Universita¨ tsmedizin Berlin, corporate member of Freie Universita¨ t Berlin, Humboldt-Universita¨ t zu Berlin, and Berlin Institute of Health, Berlin, Germany; 2Freie Universita¨ t Berlin, Institut fu¨ r Biologie, Berlin, Germany; 3Leibniz-Forschungsinstitut fu¨ r Molekulare Pharmakologie (FMP), Berlin, Germany; 4NeuroCure Cluster of Excellence, Berlin, Germany; 5DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany; 6Neuroscience Research Center, Charite´ – Universita¨ tsmedizin Berlin, corporate member of Freie Universita¨ t Berlin, Humboldt-Universita¨ t zu Berlin, and Berlin Institute of Health, Berlin, Germany Abstract All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across *For correspondence: different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in [email protected] (SJS); neurotransmitter release at different central murine synapses and thus contributes to synaptic [email protected] diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on (CR); neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal [email protected] (DS) mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting †These authors contributed vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active equally to this work zone.
    [Show full text]
  • G-Protein-Coupled Receptors in CNS: a Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits
    cells Review G-Protein-Coupled Receptors in CNS: A Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits Shofiul Azam 1 , Md. Ezazul Haque 1, Md. Jakaria 1,2 , Song-Hee Jo 1, In-Su Kim 3,* and Dong-Kug Choi 1,3,* 1 Department of Applied Life Science & Integrated Bioscience, Graduate School, Konkuk University, Chungju 27478, Korea; shofi[email protected] (S.A.); [email protected] (M.E.H.); md.jakaria@florey.edu.au (M.J.); [email protected] (S.-H.J.) 2 The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia 3 Department of Integrated Bioscience & Biotechnology, College of Biomedical and Health Science, and Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Korea * Correspondence: [email protected] (I.-S.K.); [email protected] (D.-K.C.); Tel.: +82-010-3876-4773 (I.-S.K.); +82-43-840-3610 (D.-K.C.); Fax: +82-43-840-3872 (D.-K.C.) Received: 16 January 2020; Accepted: 18 February 2020; Published: 23 February 2020 Abstract: Neurodegenerative diseases are a large group of neurological disorders with diverse etiological and pathological phenomena. However, current therapeutics rely mostly on symptomatic relief while failing to target the underlying disease pathobiology. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system (CNS) disorders. Many currently available antipsychotic therapeutics also act as either antagonists or agonists of different GPCRs. Therefore, GPCR-based drug development is spreading widely to regulate neurodegeneration and associated cognitive deficits through the modulation of canonical and noncanonical signals.
    [Show full text]