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2 edition of Oligomerization of the D2 dopamine receptor. found in the catalog.

Oligomerization of the D2 dopamine receptor.

Samuel Paikwon Lee

Oligomerization of the D2 dopamine receptor.

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Written in English


About the Edition

Dopamine is the predominant catecholamine neurotransmitter in the brain, where it controls numerous functions. The physiological actions of dopamine are mediated by five G protein-coupled receptors (GPCRs). The D2 dopamine receptor (D2DR) is the model receptor of D2-like subfamily of dopamine receptors and is prototypic of GPCRs that inhibit adenylyl cyclase and activate K+ channels.Taken together, these studies represent a significant characterization of both the function and structure of D2DR oligomerization. The realization that oligomerization is a pivotal aspect of GPCR biology with implications for trafficking, signalling, and pharmacology has provided more intricate models for understanding the physiological roles of these receptors and prompted a re-evaluation of established ideas. The determinations for D2DR oligomers in this study may yield clues to the principles governing the oligomerization of all rhodopsin-like GPCRs and thereby a better understanding of these important proteins.Initial biochemical characterization of D2DR dimerization revealed that there was a robust interaction between receptor monomers that could not be dissociated by chaotropic agents. Further, neither agonist nor antagonist binding to the D2DR affected the extent of receptor dimerization. Interestingly, co-expression of the wild-type D2DR with truncation mutants and some point mutants of the D2DR resulted in inhibition of cell surface expression of the receptor as the result of an interaction between the receptor mutant and the D2DR. This finding suggested that oligomerization of the receptor occurred prior to cell surface trafficking and that a properly arranged oligomeric complex was required for D2DR trafficking. An investigation of the structural assembly of dimeric receptors showed that there are several sites of interaction including transmembrane domain interactions. Specifically, a symmetrical transmembrane domain 4 interface was identified as being one of these sites.Until recently, it has been assumed that GPCRs function as monomers. However, it has become well established that GPCRs can form dimers and oligomers, leading to a re-evaluation of the mechanisms thought to mediate GPCR function. This thesis documents the characterization of the functional role of D2DR homo-oligomers and elucidation of the sites of intermolecular association in D2DR homodimers. It includes experiments performed prior to the first widely accepted published reports on GPCR dimerization and during the explosive period of research when theories concerning oligomerization evolved rapidly.

The Physical Object
Pagination275 leaves.
Number of Pages275
ID Numbers
Open LibraryOL19512189M
ISBN 10061294557X

G protein-coupled receptor (GPCR)-mediated signal transduction has been studied for more than a century. Despite the intense focus on this class of proteins, a molecular understanding of what constitutes the functional form of the receptor is still uncertain. GPCRs have traditionally been conceptualized as monomeric proteins, and this view has changed little over the years until relatively.   Abstract. The existence of dimers and oligomers for many G protein-coupled receptors has been described by us and others. Since many G protein-coupled receptor subtypes are highly homologous to each other, we examined whether closely related receptors may interact with each other directly and thus have the potential to create novel signaling units.


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Oligomerization of the D2 dopamine receptor. by Samuel Paikwon Lee Download PDF EPUB FB2

Abstract. Each dopamine (DA) receptor subtype physically interacts with its own kind (homomers) or other receptors (heteromers) in the plasma membrane of neurons in the basal ganglia to form dimeric or high-order receptor oligomers, termed dimeric or high-order receptor mosaics (RMs).Cited by: 2.

A GPCR oligomer is a protein complex that consists of a small number (ὀλίγοι oligoi "a few", μέρος méros "part, piece, component") of G protein-coupled receptors (GPCRs).

It is held together by covalent bonds or by intermolecular subunits within this complex are called protomers, while unconnected receptors are called monomers. Receptor homomers consist of identical. Dopamine receptors are among the most validated drug targets for neuropsychiatric disorders such as schizophrenia and Parkinson’s disease, and are potential targets for other disorders such as substance abuse, depression, Tourette’s syndrome, and attention deficit hyperactivity disorder.

As sites of action for drugs used to treat schizophrenia and Parkinson’s disease, dopamine receptors are among the most validated drug targets for neuropsychiatric disorders. Dopamine receptors are also drug targets or potential targets for other disorders such as substance abuse, depression.

As sites of action for drugs used to treat schizophrenia and Parkinson’s disease, dopamine receptors are among the most validated drug targets for neuropsychiatric disorders. Dopamine receptors are also drug targets or potential targets for other disorders such as substance abuse, depression, Tourette’s syndrome, and attention deficit hyperactivity disorder.

Download: Download full-size image Figure Relationship of dopamine receptor signal transduction pathways. Dopamine binds to dopamine receptors (DARs) to cause the exchange of GTP for GDP at the G α subunit and the dissociation of G βγ, which goes on to interact with effectors like ion channels.G α hydrolyzes GTP (with the help of RGS proteins in the case of G αi and G αq family.

Ng GYK, O'Dowd BF, Lee SP, Chung HT, Brann MR, Seeman P, George SR () Dopamine D2 receptor dimers and receptor-blocking peptides.

Biochem Biophys Res Commun – [ PubMed ] Overton MC, Blumer KJ () The extracellular N-terminal domain and transmembrane domains 1 and 2 mediate oligomerization of a yeast G protein-coupled by: Jussi Hirvonen, Jarmo Hietala, in Imaging of the Human Brain in Health and Disease, Dopamine D 1 Receptor Imaging in Schizophrenia.

Cortical dopamine D 1 receptors are crucial for working memory performance, which is disturbed in schizophrenia (Goldman-Rakic et al., ; Sawaguchi and Goldman-Rakic, ).These receptors are located in apical dendrites and spines of.

It is important to stress that up to 80% of NAc cholinergic interneurons also express D2 dopamine recep37,38,39, and their selective activation enhances phasic dopamine release in Cited by: Dopamine D2 receptors (D2R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of schizophrenia.

Pharmacological targeting and modulation of the equilibrium of these receptor homodimers might lead to a better understanding of the critical role played by these complexes in physiological and pathological by: 5. Dopamine’s actions are mediated by a family of five G-protein coupled receptors (GPCRs) (viz.

D1, D2, D3, D4 and D5)¹. The D2 dopamine receptor (DRD2) is the primary target for both typical². Dopamine D4 receptors (D4Rs) are G protein-coupled receptors that play a role in attention and cognition.

In the present study, we investigated the dimerization properties of this receptor. Receptor oligomerization in family B1 of G-protein-coupled receptors: focus on BRET investigations and the link between GPCR oligomerization and binding cooperativity.

Front. Endocrinol. D2/D3 dopamine receptor heterodimers exhibit unique functional properties. by: The D2 dopamine receptor is a G protein-coupled receptor located on postsynaptic dopaminergic neurons that is centrally involved in reward-mediating mesocorticolimbic pathways (Neville et al., ).The DRD2 gene encodes encodes 2 molecularly distinct isoforms with distinct functions (Usiello et al., ).Signaling through dopamine D2 receptors governs physiologic functions related to.

ISBN: OCLC Number: Description: 1 online resource: v.: digital: Contents: Historical Overview/Introduction to the Dopamine Receptors --Gene and Promoter Structures of the Dopamine Receptors --Structural Basis of Dopamine Receptor Activation and Function --Dopamine Receptor Subtype-Selective Drugs: D2-like Receptors --Dopamine Receptor Subtype.

Oligomers of D2 dopamine receptors Oligomers of D2 dopamine receptors Strange, Philip There is increasing evidence that G protein-coupled receptors form oligomers and that this might be important for their function.

We have studied this phenomenon for the D2 dopamine receptor and have shown—using a variety of biochemical and biophysical techniques—that this. G protein-coupled receptor (GPCR)-mediated signal transduction has been studied for more than a century.

Despite the intense focus on this class of proteins, a molecular understanding of what constitutes the functional form of the receptor is still uncertain. GPCRs have traditionally been conceptualized as monomeric proteins, and this view has changed little over the years until relatively Cited by: Get this from a library.

The dopamine receptors. [Kim A Neve;] -- As sites of action for drugs used to treat schizophrenia and Parkinson's disease, dopamine receptors are among the most validated drug targets for neuropsychiatric disorders.

Dopamine receptors are. Effect of D2 receptor agonist, quinpirole, on the desensitization 75 of the D1-D2 receptor heteromer mediated calcium signal in HEK T cells stably expressing D1 and D2 receptors.

Figure Specificity of dopamine receptor agonists activating the 76 D1-D2 receptor heteromer calcium signal in Author: Vaneeta Verma.

Purchase Oligomerization and Allosteric Modulation in G-Protein Coupled Receptors, Volume - 1st Edition. Print Book & E-Book. ISBNOligomerization in Health and Disease: From Enzymes to G Protein-Coupled Receptors, Volume in the Progress in Molecular Biology and Translational Science series, provides in-depth reviews on topics of exceptional scientific importance.

Topics of note in this new release include Computational prediction and re-design of aberrant oligomerization, Oligomerization of G protein-coupled. KEYWORDS: dopamine receptor, heterooligomer, D1 dopamine receptor, D2 dopamine receptor, G protein coupled receptor, calcium signal, Gq, oligomerization, striatum, drug addiction, schizophrenia INTRODUCTION The analysis of the range of mechanisms of protein-protein interactions has revolutionized the field of G.

processes. The amount of dopamine in the extracellular space determines the amount of dopamine signaling and is primarily controlled by two presynaptic proteins: the dopamine transporter (DAT), which removes dopamine from the extracellular space, and the D2-like dopamine autoreceptor (D 2 autoreceptor).

D 2. The role of oligomerization in D1 dopamine receptor trafficking to the cell surface was examined using conformationally distinct variants of this receptor. Substitution of the highly conserved aspartic acid (Asp) in transmembrane domain 3 resulted in a constitutively active receptor, DA, that did not bind agonists or antagonists but trafficked to the cell surface as by: 2 oligomerization in the Cath.a differentiated neuronal cell model.

Receptor fusions to BiFC fluorescent protein fragments retained their function when expressed alone, or in A 2A/A 2A, D 2/D 2, and A 2A/D 2 BiFC pairs. Robust fluorescence complementation reflecting A 2A/D 2 heteromers was detected at the cell membrane as well as in endosomes Cited by: Dopamine Receptor Oligomerization Kjell Fuxe, Daniel Marcellino, Diego Guidolin, Amina Woods and Luigi Agnati Dopamine Receptor Modulation of Glutamatergic Neurotransmission Carlos Cepeda, Véronique M.

André, Emily L. Jocoy and Michael S. Levine Unraveling the Role of Dopamine Receptors in vivo: Lessons from Knockout MicePrice: $ From the book reviews: “Designed for active researchers ranging from students to established scientists, the book is edited by a proteomics researcher working the in the area of dopamine and nicotine receptor protein interaction networks.

this book adds a collection of methods for contemporary techniques that should prove useful to researchers wishing to apply these approaches to their. dopamine and the dopamine receptors. A milestone was the suggestion by Cools and Van Rossum, based on anatomical, electrophysiological and pharmacological studies, that there might be more than one kind of receptor for dopamine in the brain.3 Biochemical studies on dopamine receptors in theFile Size: KB.

The five muscarinic acetylcholine receptors (M1–M5) are prototypical members of the superfamily of G-protein-coupled receptors (GPCRs).

During the. Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. View protein in InterPro IPR Dopamine_D2_rcpt IPR Dopamine_rcpt IPR GPCR_Rhodpsn IPR GPCR_Rhodpsn_7TM: Pfam i: View protein in Pfam PF 7tm_1, 1 hit PRINTS i: PR D 1 and D 5 receptors (also known as D 1-like receptors) are a subset of the dopamine receptor G-protein-coupled receptor family that also includes D 2, D 3 and D two receptor subtypes are highly homologous and very few ligands have been identified that are selective between the D 1 and D 5 subtypes.

D 1 receptors are widely expressed throughout the brain, whereas D 5 receptors show a. For the dopamine regulation experiments, the cell cultures grown overnight were treated with dopamine ( µ m) in the presence of m m sodium metabisulfite (to prevent oxidization of dopamine in the culture medium), and cells were harvested at selected intervals up to 24 by: Across the 3 dopamine receptors, compounds 2 and 5 have the same order of potency (D 2 >D 3 >D 1).

The data shown in the table above is for compound 2. Mesoridazine is also a selective antagonist of the serotonin 5-HT 2A receptor.

Zotepine has a K i of nM for the D 2S receptor isoform. D 2 receptors are members of the dopamine receptor G-protein-coupled receptor family that also includes D 1, D 3, D 4 and D are located primarily in the caudate putamen, nucleus accumbens and olfactory tubercle where they are involved in the modulation of locomotion, reward, reinforcement and memory and human D 2 receptor gene has been localized to chromosome 11 (11q).

Dopamine receptor D2 (D2R) plays an important role in the human central nervous system and is a focal target of antipsychotic agents. The D2 High R and D2 Low R dimeric models previously developed by our group are used to investigate the prediction of binding affinity of the LY, ligand and its binding mechanism within the catalytic domain.

The computational data obtained using molecular Cited by: 5. FIGURE 1. Biochemical analysis of EMR2 oligomerization. A, the cross-linking experiment indicates that EMR2-FL is closely associated on the cell surface of transfected -K1 cells transfected with an empty vector (lanes 1 and 2) or EMR2-FL (lanes 3 and 4) were treated with (lanes 2 and 4) or without 1 m m BS 3 (lanes 1 and 3) and analyzed for EMR2 expression by Western.

Fig. A) 3D structure of the human dopamine D2 receptor. B) Ramachandran plot for the human dopamine D2 receptor. The final model has % amino acids in the most favorable regions, while the other % amino acids are placed in the additional allowed regions of the Ramachandran : Liliana Ostopovici-Halip, Ramona Rad-Curpan.

The ability of G protein coupled receptors to heterooligomerize and create novel signaling complexes has demonstrated the tremendous potential of these receptors to access diverse signaling cascades, as well as to modulate the nature of the transduced signal.

In the dopamine receptor field, the existence of a D1-like receptor in brain that activated phospatidylinositol turnover has been shown Cited by: Class A GPCR oligomerization Chapter 8 Class A GPCR oligomerization: reasons of controversy Salvador Sierra, Rudy Toneatti and Javier Gonza´lez-Maeso Department of.

The D2 receptor prevents potentiation of glutamate responses in the ventral tegmental area (VTA) neurons. Repeated cocaine treatment causes loss of D2 dopamine receptor functional responses, which is one mechanism of cocaine-induced pleasure/addiction.

It's better to have this gene increased most of the time. Exceptions: psychosis, schizophrenia. The researchers found that the dopamine D2 receptor gene (D2R) significantly influences lifespan, body weight and locomotor activity, but only when combined with an enriched environment that included social interaction, sensory and cognitive stimulation and, most critically, exercise.This gene encodes the D2 subtype of the dopamine receptor.

This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia\; other mutations have been associated with schizophrenia.Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and by: