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https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#1
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28215100/targeting-baff-and-april-in-systemic-lupus-erythematosus-and-other-antibody-associated-diseases
#2
Eileen Samy, Stephen Wax, Bertrand Huard, Henry Hess, Pascal Schneider
The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials...
January 2, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28193731/selective-transport-of-neurotransmitters-and-modulators-by-distinct-volume-regulated-lrrc8-anion-channels
#3
Darius Lutter, Florian Ullrich, Jennifer C Lueck, Stefan Kempa, Thomas J Jentsch
In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine...
February 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28187919/dopamine-d3-and-acetylcholine-nicotinic-receptor-heteromerization-in-midbrain-dopamine-neurons-relevance-for-neuroplasticity
#4
Leonardo Bontempi, Paola Savoia, Federica Bono, Chiara Fiorentini, Cristina Missale
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer(2) (BRET(2)) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET(2) showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR...
February 7, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28187393/shape-controlled-fabrication-of-magnetite-silver-hybrid-nanoparticles-with-high-performance-magnetic-hyperthermia
#5
Qi Ding, Dongfang Liu, Dawei Guo, Fang Yang, Xingyun Pang, Renchao Che, Naizhen Zhou, Jun Xie, Jianfei Sun, Zhihai Huang, Ning Gu
Superparamagnetic Fe3O4 nanoparticles (NPs)-based hyperthermia is a promising non-invasive approach for cancer therapy. However, the heat transfer efficiency of Fe3O4 NPs is relative low, which hinders their practical clinical applications. Therefore, it is promising to improve the magnetic hyperthermia efficiency by exploring the higher performance magnetic NPs-based hybrid nanostructures. In the current study, it presents a straightforward in situ reduction method for the shape-controlled preparation of magnetite (Fe3O4) silver (Ag) hybrid NPs designed as magnetic hyperthermia heat mediators...
January 31, 2017: Biomaterials
https://www.readbyqxmd.com/read/28139906/heteromer-induction-an-approach-to-unique-pharmacology
#6
Philip S Portoghese, Eyup Akgün, Mary M Lunzer
It is proposed that two types of opioid receptor heteromers exist: a) those that are constitutive and b) those that are induced by bivalent ligands. Mu opioid agonists interact with constitutive MOR-DOR heteromer to mediate tolerance and dependence. Bivalent ligand, MDAN21, is devoid of these adverse effects by virtue of its DOR antagonist pharmacophore. We propose that bivalent ligands MMG22 and MCC22 induce colocalized receptors to form heteromers (MOR-mGluR5 and MOR-CCR5, respectively) that do not occur naturally, thereby promoting unique pharmacology...
January 31, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28121479/cisplatin-activates-volume-sensitive-lrrc8-channel-mediated-currents-in-xenopus-oocytes
#7
Antonella Gradogna, Héctor Gaitán-Peñas, Anna Boccaccio, Raúl Estévez, Michael Pusch
LRRC8 proteins have been shown to underlie the ubiquitous volume regulated anion channel (VRAC). VRAC channels are composed of the LRRC8A subunit and at least one among the LRRC8B-E subunits. In addition to their role in volume regulation, LRRC8 proteins have been implicated in the uptake of chemotherapeutic agents. We had found that LRRC8 channels can be conveniently expressed in Xenopus oocytes, a system without endogenous VRAC activity. The fusion with fluorescent proteins yielded constitutive activity for A/C, A/D and A/E heteromers...
January 25, 2017: Channels
https://www.readbyqxmd.com/read/28119185/genetic-variants-of-dopamine-d2-receptor-impact-heterodimerization-with-dopamine-d1-receptor
#8
Ewa Błasiak, Sylwia Łukasiewicz, Kinga Szafran-Pilch, Marta Dziedzicka-Wasylewska
BACKGROUND: The human dopamine D2 receptor gene has three polymorphic variants that alter its amino acid sequence: alanine substitution by valine in position 96 (V96A), proline substitution by serine in position 310 (P310S) and serine substitution by cysteine in position 311 (S311C). Their functional role has never been the object of extensive studies, even though there is some evidence that their occurrence correlates with schizophrenia. METHODS: The HEK293 cell line was transfected with dopamine D1 and D2 receptors (or genetic variants of the D2 receptor), coupled to fluorescent proteins which allowed us to measure the extent of dimerization of these receptors, using a highly advanced biophysical approach (FLIM-FRET)...
October 29, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28115188/impact-of-g-protein-coupled-receptor-heteromers-in-endocrine-systems
#9
K C Jonas, A C Hanyaloglu
The fine-tuning of endocrine homeostasis is regulated by dynamic receptor mediated processes. The superfamily of G protein-coupled receptors (GPCRs) have diverse roles in the modulation of all endocrine axes, thus understanding the mechanisms underpinning their functionality is paramount for treatment of endocrinopathies. Evidence over the last 20 years has highlighted homo and heteromerization as a key mode of mediating GPCR functional diversity. This review will discuss the concept of GPCR heteromerization and its relevance to endocrine function, detailing in vitro and in vivo evidence, and exploring current and potential pharmacological strategies for specific targeting of GPCR heteromers in endocrine heath and disease...
January 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#10
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
#11
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
#12
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
#13
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...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28066150/calcium-permeability-of-transient-receptor-potential-canonical-trpc-4-channels-measured-by-trpc4-gcamp6s
#14
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
#15
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
#16
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
#17
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 (TRPC4) protein. Because these channels are Ca(2+)-permeable, it was initially thought that the cytotoxicity arose as a consequence of Ca(2+) 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 Ca(2+) elevation, TRPC1 was not...
January 13, 2017: 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
#18
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
#19
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
#20
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
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