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https://www.readbyqxmd.com/read/29053217/behavioral-control-by-striatal-a2a-dopamine-d2-receptor-heteromers
#1
Jaume Taura, Marta Valle-León, Kristoffer Sahlholm, Masahiko Watanabe, Katheleen Van Craenenbroeck, Víctor Fernández-Dueñas, Sergi Ferré, Francisco Ciruela
G protein-coupled receptors (GPCR) exhibit the ability to form receptor complexes that include molecularly different GPCR (i.e. GPCR heteromers), which endow them with singular functional and pharmacological characteristics. The relative expression of GPCR heteromers remains a matter of intense debate. Recent studies support that adenosine A2A receptors (A2A R) and dopamine D2 receptors (D2 R) predominantly form A2A R-D2 R heteromers in the striatum. The aim of the present study was evaluating the behavioral effects of pharmacological manipulation and genetic blockade of A2A R and D2 R within the frame of such a predominant striatal heteromeric population...
October 20, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29026145/cibinetide-dampens-innate-immune-cell-functions-thus-ameliorating-the-course-of-experimental-colitis
#2
Manfred Nairz, David Haschka, Stefanie Dichtl, Thomas Sonnweber, Andrea Schroll, Malte Aßhoff, John E Mindur, Patrizia L Moser, Dominik Wolf, Filip K Swirski, Igor Theurl, Anthony Cerami, Michael Brines, Günter Weiss
Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (CD131) form heteromers (the innate repair receptor; IRR), and exert tissue protective effects. We used dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis was established, mice were treated with solvent, EPO or the selective IRR agonist cibinetide...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935133/functional-validation-of-heteromeric-kainate-receptor-models
#3
Teresa Paramo, Patricia M G E Brown, Maria Musgaard, Derek Bowie, Philip C Biggin
Kainate receptors require the presence of external ions for gating. Most work thus far has been performed on homomeric GluK2 but, in vivo, kainate receptors are likely heterotetramers. Agonists bind to the ligand-binding domain (LBD) which is arranged as a dimer of dimers as exemplified in homomeric structures, but no high-resolution structure currently exists of heteromeric kainate receptors. In a full-length heterotetramer, the LBDs could potentially be arranged either as a GluK2 homomer alongside a GluK5 homomer or as two GluK2/K5 heterodimers...
September 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28883043/ffar2-ffar3-receptor-heteromerization-modulates-short-chain-fatty-acid-sensing
#4
Zhiwei Ang, Ding Xiong, Min Wu, Jeak Ling Ding
Free fatty acid receptors (FFAR2/FFA2/GPR43 and FFAR3/FFA3/GPR41) are mammalian receptors for gut microbiota-derived short-chain fatty acids (SCFAs). These receptors are promising drug targets for obesity, colitis, colon cancer, asthma, and arthritis. Here, we demonstrate that FFAR2 and FFAR3 interact to form a heteromer in primary human monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28862946/%C3%AE-1-adrenergic-receptors-function-within-hetero-oligomeric-complexes-with-atypical-chemokine-receptor-3-and-chemokine-c-x-c-motif-receptor-4-in-vascular-smooth-muscle-cells
#5
Lauren J Albee, Jonathan M Eby, Abhishek Tripathi, Heather M LaPorte, Xianlong Gao, Brian F Volkman, Vadim Gaponenko, Matthias Majetschak
BACKGROUND: Recently, we provided evidence that α1-adrenergic receptors (ARs) in vascular smooth muscle are regulated by chemokine (C-X-C motif) receptor (CXCR) 4 and atypical chemokine receptor 3 (ACKR3). While we showed that CXCR4 controls α1-ARs through formation of heteromeric receptor complexes in human vascular smooth muscle cells (hVSMCs), the molecular basis underlying cross-talk between ACKR3 and α1-ARs is unknown. METHODS AND RESULTS: We show that ACKR3 agonists inhibit inositol trisphosphate production in hVSMCs on stimulation with phenylephrine...
August 17, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28843453/receptor-heteromer-mediated-regulation-of-endocannabinoid-signaling-in-activated-microglia-role-of-cb1-and-cb2-receptors-and-relevance-for-alzheimer-s-disease-and-levodopa-induced-dyskinesia
#6
Gemma Navarro, Dasiel Borroto-Escuela, Edgar Angelats, Íñigo Etayo, Irene Reyes-Resina, Marta Pulido-Salgado, Ana I Rodriguez-Perez, Enric I Canela, Josep Saura, José Luis Lanciego, José Luis Labandeira-García, Carlos A Saura, Kjell Fuxe, Rafael Franco
Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. Unlike CB1, CB2 receptors and CB1-CB2Hets were upregulated in activated microglia...
August 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28842490/a-conserved-c-terminal-rxg-motif-in-the-ngbr-subunit-of-cis-prenyltransferase-is-critical-for-prenyltransferase-activity
#7
Kariona A Grabińska, Ban H Edani, Eon Joo Park, Jan R Kraehling, William C Sessa
cis-Prenyltransferases (cis-PTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. In eukaryotes and archaea, cis-PT is the first enzyme committed to the synthesis of dolichyl phosphate, an obligate lipid carrier in protein glycosylation reactions. The homodimeric bacterial enzyme, undecaprenyl diphosphate synthase, generates 11 isoprene units and has been structurally and mechanistically characterized in great detail. Recently, we discovered that unlike undecaprenyl diphosphate synthase, mammalian cis-PT is a heteromer consisting of NgBR (Nus1) and hCIT (dehydrodolichol diphosphate synthase) subunits, and this composition has been confirmed in plants and fungal cis-PTs...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28841766/subunit-dependent-oxidative-stress-sensitivity-of-lrrc8-volume-regulated-anion-channels
#8
Antonella Gradogna, Paola Gavazzo, Anna Boccaccio, Michael Pusch
KEY POINTS: Swelling-activated anion currents are modulated by oxidative conditions, but it is unknown if oxidation acts directly on the LRRC8 channel-forming proteins or on regulatory factors. We found that LRRC8A-LRRC8E heteromeric channels are dramatically activated by oxidation of intracellular cysteines, whereas LRRC8A-LRRC8C and LRRC8A-LRRC8D heteromers are inhibited by oxidation. Volume-regulated anion currents in Jurkat T lymphocytes were inhibited by oxidation, in agreement with a low expression of the LRRC8E subunit in these cells...
November 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28829739/allosteric-control-of-an-asymmetric-transduction-in-a-g-protein-coupled-receptor-heterodimer
#9
Junke Liu, Zongyong Zhang, David Moreno-Delgado, James Ar Dalton, Xavier Rovira, Ana Trapero, Cyril Goudet, Amadeu Llebaria, Jesús Giraldo, Qilin Yuan, Philippe Rondard, Siluo Huang, Jianfeng Liu, Jean-Philippe Pin
GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD...
August 10, 2017: ELife
https://www.readbyqxmd.com/read/28827538/orphan-gpr61-gpr62-and-gpr135-receptors-and-the-melatonin-mt2-receptor-reciprocally-modulate-their-signaling-functions
#10
Atsuro Oishi, Angeliki Karamitri, Romain Gerbier, Olivier Lahuna, Raise Ahmad, Ralf Jockers
Understanding the function of orphan G protein-coupled receptors (GPCRs), whose cognate ligand is unknown, is of major importance as GPCRs are privileged drug targets for many diseases. Recent phylogenetic studies classified three orphan receptors, GPR61, GPR62 and GPR135 among the melatonin receptor subfamily, but their capacity to bind melatonin and their biochemical functions are not well characterized yet. We show here that GPR61, GPR62 and GPR135 do not bind [(3)H]-melatonin nor 2-[(125)I]iodomelatonin and do not respond to melatonin in several signaling assays...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28734930/bidirectional-allosteric-interactions-between-cannabinoid-receptor-1-cb1-and-dopamine-receptor-2-long-d2l-heterotetramers
#11
Amina M Bagher, Robert B Laprairie, J Thomas Toguri, Melanie E M Kelly, Eileen M Denovan-Wright
Type 1 cannabinoid (CB1) and dopamine 2 long form (D2L) receptors can physically interact to form heteromers that display unique pharmacology in vitro compared to homomeric complexes. Co-expression of CB1 and D2L and co-application of CB1 and D2 agonists increases cAMP levels while administration of either agonist alone decreases cAMP levels. To understand the observed co-agonist response, our first goal of the current study was to define the stoichiometry of CB1/D2L/Gα protein complexes. Using bioluminescence resonance energy transfer 2 (BRET(2)), we confirmed that, CB1 homodimers, D2L homodimers, and CB1/D2L heteromers are formed...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28705698/receptor-activity-modifying-protein-dependent-and-independent-activation-mechanisms-in-the-coupling-of-calcitonin-gene-related-peptide-and-adrenomedullin-receptors-to-gs
#12
Michael J Woolley, Christopher A Reynolds, John Simms, Christopher S Walker, Juan Carlos Mobarec, Michael L Garelja, Alex C Conner, David R Poyner, Debbie L Hay
Calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors are heteromers of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, and one of three receptor activity-modifying proteins (RAMPs). How CGRP and AM activate CLR and how this process is modulated by RAMPs is unclear. We have defined how CGRP and AM induce Gs-coupling in CLR-RAMP heteromers by measuring the effect of targeted mutagenesis in the CLR transmembrane domain on cAMP production, modeling the active state conformations of CGRP and AM receptors in complex with the Gs C-terminus and conducting molecular dynamics simulations in an explicitly hydrated lipidic bilayer...
October 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28701349/actin-cytoskeleton-dependent-regulation-of-corticotropin-releasing-factor-receptor-heteromers
#13
Burcu Hasdemir, Shilpi Mahajan, Juan Oses-Prieto, Shreya Chand, Michael Woolley, Alma Burlingame, Dimitris K Grammatopoulos, Aditi Bhargava
Stress responses are highly nuanced and variable, but how this diversity is achieved by modulating receptor function is largely unknown. Corticotropin-releasing factor receptors (CRFRs), class B G protein-coupled receptors, are pivotal in mediating stress responses. Here we show that the two known CRFRs interact to form heteromeric complexes in HEK293 cells coexpressing both CRFRs and in vivo in mouse pancreas. Coimmunoprecipitation and mass spectrometry confirmed the presence of both CRF1R and CRF2βR, along with actin in these heteromeric complexes...
September 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28630296/subunit-specific-role-for-the-amino-terminal-domain-of-ampa-receptors-in-synaptic-targeting
#14
Javier Díaz-Alonso, Yujiao J Sun, Adam J Granger, Jonathan M Levy, Sabine M Blankenship, Roger A Nicoll
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28622290/structural-basis-for-the-regulatory-interactions-of-proapoptotic-par-4
#15
Udaya K Tiruttani Subhramanyam, Jan Kubicek, Ulf B Eidhoff, Joerg Labahn
Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization...
September 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28620024/signalling-assemblies-the-odds-of-symmetry
#16
REVIEW
Gábor Maksay, Joseph A Marsh
The assembly of proteins into complexes is fundamental to nearly all biological signalling processes. Symmetry is a dominant feature of the structures of experimentally determined protein complexes, observed in the vast majority of homomers and many heteromers. However, some asymmetric structures exist, and asymmetry also often forms transiently, intractable to traditional structure determination methods. Here, we explore the role of protein complex symmetry and asymmetry in cellular signalling, focusing on receptors, transcription factors and transmembrane channels, among other signalling assemblies...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28608532/heteromers-of-%C3%AE-opioid-and-dopamine-d1-receptors-modulate-opioid-induced-locomotor-sensitization-in-a-dopamine-independent-manner
#17
Yi-Min Tao, Chuan Yu, Wei-Sheng Wang, Yuan-Yuan Hou, Xue-Jun Xu, Zhi-Qiang Chi, Yu-Qiang Ding, Yu-Jun Wang, Jing-Gen Liu
BACKGROUND AND PURPOSE: Exposure to opiates induces locomotor sensitization in rodents, which has been proposed to correspond to the compulsive drug-seeking behaviour. Numerous studies have demonstrated that locomotor sensitization can occur in a dopamine transmission-independent manner; however, the underlying mechanisms are unclear. EXPERIMENTAL APPROACH: Co-immunoprecipitation, BRET and cross-antagonism assays were used to demonstrate the existence of receptor heterodimers...
September 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28580231/hormones-and-neuropeptide-receptor-heteromers-in-the-ventral-tegmental-area-targets-for-the-treatment-of-loss-of-control-of-food-intake-and-substance-use-disorders
#18
REVIEW
Sergi Ferré
Hormones and neuropeptides represent biological correlates of internal homeostatic signals detected and integrated in the hypothalamus, which establishes a robust functional connection with the ventral tegmental area (VTA). The hypothalamus-VTA connection determines the ability of these signals to influence central dopaminergic neurotransmission and, therefore, their ability to increase responsiveness to their reward-associated stimuli and to establish appropriate associative learning. The hypothalamus also provides the main source of the multiple neuropeptides that are released in the VTA...
2017: Current Treatment Options in Psychiatry
https://www.readbyqxmd.com/read/28561759/heteromer-nanostars-by-spontaneous-self-assembly
#19
Caitlin Brocker, Hannah Kim, Daniel Smith, Sutapa Barua
Heteromer star-shaped nanoparticles have the potential to carry out therapeutic agents, improve intracellular uptake, and safely release drugs after prolonged periods of residence at the diseased site. A one-step seed mediation process was employed using polylactide-co-glycolic acid (PLGA), polyvinyl alcohol (PVA), silver nitrate, and tetrakis(hydroxymethyl)phosphonium chloride (THPC). Mixing these reagents followed by UV irradiation successfully produced heteromer nanostars containing a number of arm chains attached to a single core with a high yield...
May 31, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28503149/vascular-kinin-b1-and-b2-receptors-determine-endothelial-dysfunction-through-neuronal-nitric-oxide-synthase
#20
Thássio R R Mesquita, Gianne P Campos-Mota, Virgínia S Lemos, Jader S Cruz, Itamar C G de Jesus, Enilton A Camargo, Jorge L Pesquero, João B Pesquero, Luciano Dos Santos A Capettini, Sandra Lauton-Santos
B1- and B2-kinin receptors are G protein-coupled receptors that play an important role in the vascular function. Therefore, the present study was designed to evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced vascular relaxation, focusing on the protein-protein interaction involving kinin receptors with endothelial and neuronal nitric oxide synthases (eNOS and nNOS). Vascular reactivity, nitric oxide (NO·) and reactive oxygen species (ROS) generation, co-immunoprecipitation were assessed in thoracic aorta from male wild-type (WT), B1- (B1R(-/-)), B2- (B2R(-/-)) knockout mice...
2017: Frontiers in Physiology
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