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https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#1
Estefanía Moreno, Anna Chiarlone, Mireia Medrano, Mar Puigdellívol, Lucka Bibic, Lesley A Howell, Eva Resel, Nagore Puente, María J Casarejos, Juan Perucho, Joaquín Botta, Nuria Suelves, Francisco Ciruela, Silvia Ginés, Ismael Galve-Roperh, Vicent Casadó, Pedro Grandes, Beat Lutz, Krisztina Monory, Enric I Canela, Carmen Lluís, Peter J McCormick, Manuel Guzmán
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28098160/a-zip6-zip10-heteromer-controls-ncam1-phosphorylation-and-integration-into-focal-adhesion-complexes-during-epithelial-to-mesenchymal-transition
#2
Dylan Brethour, Mohadeseh Mehrabian, Declan Williams, Xinzhu Wang, Farinaz Ghodrati, Sepehr Ehsani, Elizabeth A Rubie, James R Woodgett, Jean Sevalle, Zhengrui Xi, Ekaterina Rogaeva, Gerold Schmitt-Ulms
The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087443/an-update-on-the-physiological-and-therapeutic-relevance-of-gpcr-oligomers
#3
REVIEW
Batoul Farran
The traditional view on GPCRs held that they function as single monomeric units composed of identical subunits. This notion was overturned by the discovery that GPCRs can form homo- and hetero-oligomers, some of which are obligatory, and can further assemble into receptor mosaics consisting of three or more protomers. Oligomerisation exerts significant impacts on receptor function and physiology, offering a platform for the diversification of receptor signalling, pharmacology, regulation, crosstalk, internalization and trafficking...
January 11, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28069442/novel-signaling-of-dynorphin-at-%C3%AE%C2%BA-opioid-receptor-bradykinin-b2-receptor-heterodimers
#4
Bingyuan Ji, Haiqing Liu, Rumin Zhang, Yunlu Jiang, Chunmei Wang, Sheng Li, Jing Chen, Bo Bai
The κ-opioid receptor (KOR) and bradykinin B2 receptor (B2R) are involved in a variety of important physiological processes and share many similar characteristics in terms of their distribution and functions in the nervous system. We first demonstrated the endogenous expression of KOR and B2R in human SH-SY5Y cells and their co-localization on the membrane of human embryonic kidney 293 (HEK293) cells. Bioluminescence and fluorescence resonance energy transfer and the proximity ligation assay were exploited to demonstrate the formation of functional KOR and B2R heteromers in transfected cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28066150/calcium-permeability-of-transient-receptor-potential-canonical-trpc-4-channels-measured-by-trpc4-gcamp6s
#5
Juyeon Ko, Jongyun Myeong, Dongki Yang, Insuk So
Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. A TRPC4 specific activator, (-)-englerin A, induced both current and calcium fluorescence with the similar time course...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28007761/functional-%C3%AE-opioid-galanin-receptor-heteromers-in-the-ventral-tegmental-area
#6
Estefanía Moreno, César Quiroz, William Rea, Ning-Sheng Cai, Josefa Mallol, Antoni Cortés, Carme Lluís, Enric I Canela, Vicent Casadó, Sergi Ferré
: The neuropeptide galanin has been shown to interact with the opioid system. More specifically, galanin counteracts the behavioral effects of the systemic administration of μ-opioid receptor (MOR) agonists. Yet the mechanism responsible for this galanin-opioid interaction has remained elusive. Using biophysical techniques in mammalian transfected cells we found evidence for selective heteromerization of MOR and the galanin receptor subtype Gal1 (Gal1R). Also in transfected cells, a synthetic peptide selectively disrupted MOR-Gal1R heteromerization as well as specific interactions between MOR and Gal1R ligands: a negative crosstalk, by which galanin counteracted MAPK activation induced by the endogenous MOR agonist endomorphin-1, and a cross-antagonism, by which a MOR antagonist counteracted MAPK activation induced by galanin...
December 22, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27960030/detection-of-receptor-heteromerization-using-in-situ-proximity-ligation-assay
#7
Ivone Gomes, Salvador Sierra, Lakshmi A Devi
Although G protein-coupled receptor (GPCR) heteromerization has been extensively demonstrated in vitro using heterologous cells that overexpress epitope-tagged receptors, their presence in endogenous systems is less well established. This is because a criterion to identify receptor heteromerization is the demonstration that the two interacting receptors are present not only in the same cell but also in the same subcellular compartment in close enough proximity to allow for direct receptor-receptor interaction...
December 13, 2016: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/27875305/-englerin-a-evoked-cytotoxicity-is-mediated-by-na-influx-and-counteracted-by-na-k-atpase
#8
Melanie J Ludlow, Hannah J Gaunt, Hussein N Rubaiy, Katie E Musialowski, Nicola M Blythe, Naveen S Vasudev, Katsuhiko Muraki, David J Beech
(-)-Englerin A ((-)-EA) has a rapid and potent cytotoxic effect on several types of cancer cell that is mediated by plasma membrane ion channels containing Transient Receptor Potential Canonical 4 protein (TRPC4). Since these channels are Ca2+ permeable it was initially thought that the cytotoxicity arose as a consequence of Ca2+ overload. Here we show that this is not the case and that the effect of (-)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both TRPC4 and TRPC1 were required for (-)-EA cytotoxicity, however, although TRPC4 was necessary for the (-)-EA-evoked Ca2+-elevation, TRPC1 was not...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27844101/functional-identification-of-apple-mdjaz2-in-arabidopsis-with-reduced-ja-sensitivity-and-increased-stress-tolerance
#9
Xiu-Hong An, Yu-Jin Hao, En-Mao Li, Kai Xu, Cun-Gang Cheng
Here, we report the decrease of JA-sensitivity and enhancement of tolerance to salt and PEG stresses in Arabidopsis overexpressing apple MdJAZ2. As signalling molecules, jasmonates (JAs) play significant roles in plant development and stress responses. JAZ proteins are the targets of the SCF(COI1) complex and act as the negative regulators in JA signalling pathway. However, there are no reports regarding the biological function of apple JAZ genes. In this study, one JAZ gene, MdJAZ2 from apple, was functionally characterized in detail...
November 14, 2016: Plant Cell Reports
https://www.readbyqxmd.com/read/27835800/contribution-of-heteromerization-to-g-protein-coupled-receptor-function
#10
REVIEW
Supriya A Gaitonde, Javier González-Maeso
G protein-coupled receptors (GPCRs) are a remarkably multifaceted family of transmembrane proteins that exert a variety of physiological effects. Although family A GPCRs are able to operate as monomers, there is increasing evidence that heteromerization represents a fundamental aspect of receptor function, trafficking and pharmacology. Most recently, it has been suggested that GPCR heteromers may play a crucial role as new molecular targets of heteromer-selective and bivalent ligands. The current review summarizes key recent developments in these topics...
November 8, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27773554/the-magnificent-two-histamine-and-the-h3-receptor-as-key-modulators-of-striatal-circuitry
#11
Maximiliano Rapanelli
Histaminergic dysfunction has been recently linked to tic disorders and to aberrant striatal function. There is a particular interest in the histamine 3 receptor (H3R) due to its clinical implications for treating multiple disorders and its high expression in the brain. Striatal histamine (HA) modulates through the H3R in complex ways the release of striatal neurotransmitters into this brain region. The H3R has been classically described to be coupled to Gi, although there is evidence that revealed that striatal H3R forms heteromers with the dopamine receptors 1 and 2 in the medium spiny neurons (MSNs) than changes this signaling...
February 6, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27705766/investigation-of-lrrc8-mediated-volume-regulated-anion-currents-in-xenopus-oocytes
#12
Héctor Gaitán-Peñas, Antonella Gradogna, Lara Laparra-Cuervo, Carles Solsona, Victor Fernández-Dueñas, Alejandro Barrallo-Gimeno, Francisco Ciruela, Melike Lakadamyali, Michael Pusch, Raúl Estévez
Volume-regulated anion channels (VRACs) play an important role in controlling cell volume by opening upon cell swelling. Recent work has shown that heteromers of LRRC8A with other LRRC8 members (B, C, D, and E) form the VRAC. Here, we used Xenopus oocytes as a simple system to study LRRC8 proteins. We discovered that adding fluorescent proteins to the C-terminus resulted in constitutive anion channel activity. Using these constructs, we reproduced previous findings indicating that LRRC8 heteromers mediate anion and osmolyte flux with subunit-dependent kinetics and selectivity...
October 4, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27698419/x-ray-structure-of-the-human-%C3%AE-4%C3%AE-2-nicotinic-receptor
#13
Claudio L Morales-Perez, Colleen M Noviello, Ryan E Hibbs
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century. In addition to the receptors' prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27682590/molecular-signatures-of-mu-opioid-receptor-and-somatostatin-receptor-2-in-pancreatic-cancer
#14
Raphael Jorand, Sunetra Biswas, Devin L Wakefield, Steven J Tobin, Ottavia Golfetto, Kelsey Hilton, Michelle Ko, Joe W Ramos, Alexander R Small, Peiguo Chu, Gagandeep Singh, Tijana Jovanovic-Talisman
Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein-coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, here we combine traditional biochemical approaches with superresolution microscopy methods. A novel interaction specific to PDAC is identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2)...
November 7, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27649563/signaling-modification-by-gpcr-heteromer-and-its-implication-on-x-linked-nephrogenic-diabetes-insipidus
#15
Hans K H Ng, Kaleeckal G Harikumar, Laurence J Miller, Billy K C Chow
The involvement of secretin (SCT) and secretin receptor (SCTR) in regulating body water homeostasis is well established. Identified as one of the vasopressin (Vp)-independent mechanisms in fluid balance, SCT regulates aquaporin 2 (AQP2) in the kidney distal collecting duct cells through activating intracellular cAMP production. This ability to bypass Vp-mediated water reabsorption in kidney implicates SCT's potential to treat nephrogenic diabetes insipidus (NDI). Research on NDI in the past has largely been focused on the searching for mutations in vasopressin receptor 2 (AVPR2), while the functional relationship between SCTR, AVPR2 and NDI remains unclear...
2016: PloS One
https://www.readbyqxmd.com/read/27641679/functional-recovery-of-aqp2-recessive-mutations-through-hetero-oligomerization-with-wild-type-counterpart
#16
Abdulah El Tarazi, Yoann Lussier, Sandra Da Cal, Pierre Bissonnette, Daniel G Bichet
Aquaporin-2 (AQP2) is a homotetrameric water channel responsible for the final water reuptake in the kidney. Mutations in the protein induce nephrogenic diabetes insipidus (NDI), which challenges the water balance by producing large urinary volumes. Although recessive AQP2 mutations are believed to generate non-functional and monomeric proteins, the literature identifies several mild mutations which suggest the existence of mixed wt/mut tetramers likely to carry function in heterozygotes. Using Xenopus oocytes, we tested this hypothesis and found that mild mutants (V24A, D150E) can associate with wt-AQP2 in mixed heteromers, providing clear functional gain in the process (62 ± 17% and 63 ± 17% increases, respectively), conversely to the strong monomeric R187C mutant which fails to associate with wt-AQP2...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27641494/mechanism-of-assembly-and-cooperativity-of-homomeric-and-heteromeric-metabotropic-glutamate-receptors
#17
Joshua Levitz, Chris Habrian, Shashank Bharill, Zhu Fu, Reza Vafabakhsh, Ehud Y Isacoff
G protein-coupled receptors (GPCRs) mediate cellular responses to a wide variety of extracellular stimuli. GPCR dimerization may expand signaling diversity and tune functionality, but little is known about the mechanisms of subunit assembly and interaction or the signaling properties of heteromers. Using single-molecule subunit counting on class C metabotropic glutamate receptors (mGluRs), we map dimerization determinants and define a heterodimerization profile. Intersubunit fluorescence resonance energy transfer measurements reveal that interactions between ligand-binding domains control the conformational rearrangements underlying receptor activation...
October 5, 2016: Neuron
https://www.readbyqxmd.com/read/27630107/a-novel-family-of-plant-nuclear-envelope-associated-proteins
#18
Vidya Pawar, Axel Poulet, Gwénaëlle Détourné, Christophe Tatout, Emmanuel Vanrobays, David E Evans, Katja Graumann
This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain...
October 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27624155/p2x-mediated-ampa-receptor-internalization-and-synaptic-depression-is-controlled-by-two-camkii-phosphorylation-sites-on-glua1-in-hippocampal-neurons
#19
Johan-Till Pougnet, Benjamin Compans, Audrey Martinez, Daniel Choquet, Eric Hosy, Eric Boué-Grabot
Plasticity at excitatory synapses can be induced either by synaptic release of glutamate or the release of gliotransmitters such as ATP. Recently, we showed that postsynaptic P2X2 receptors activated by ATP released from astrocytes downregulate synaptic AMPAR, providing a novel mechanism by which glial cells modulate synaptic activity. ATP- and lNMDA-induced depression in the CA1 region of the hippocampus are additive, suggesting distinct molecular pathways. AMPARs are homo-or hetero-tetramers composed of GluA1-A4...
September 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27612857/neurochemical-evidence-supporting-dopamine-d1-d2-receptor-heteromers-in-the-striatum-of-the-long-tailed-macaque-changes-following-dopaminergic-manipulation
#20
Alberto J Rico, Iria G Dopeso-Reyes, Eva Martínez-Pinilla, Diego Sucunza, Diego Pignataro, Elvira Roda, David Marín-Ramos, José L Labandeira-García, Susan R George, Rafael Franco, José L Lanciego
Although it has long been widely accepted that dopamine receptor types D1 and D2 form GPCR heteromers in the striatum, the presence of D1-D2 receptor heteromers has been recently challenged. In an attempt to properly characterize D1-D2 receptor heteromers, here we have used the in situ proximity ligation assay (PLA) in striatal sections comprising the caudate nucleus, the putamen and the core and shell territories of the nucleus accumbens. Experiments were carried out in control macaques as well as in MPTP-treated animals (with and without dyskinesia)...
September 9, 2016: Brain Structure & Function
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