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Manuel Narváez, Dasiel O Borroto-Escuela, Luis Santín, Carmelo Millón, Belén Gago, Antonio Flores-Burgess, Miguel A Barbancho, Miguel Pérez de la Mora, José Narváez, Zaida Díaz-Cabiale, Kjell Fuxe
Anxiety is evoked by a threatening situation and display adaptive or defensive behaviors, found similarly in animals and humans. Neuropeptide Y (NPY) Y1 receptor (NPYY1R) and Galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the amygdala. In a previous study, GALR2 enhanced NPYY1R mediated anxiolytic actions on spatiotemporal parameters in the open field and elevated plus maze, involving the formation of GALR2/NPYY1R heteroreceptor complexes in the amygdala. Moreover, the inclusion of complementary ethological parameters provides a more comprehensive profile on the anxiolytic effects of a treatment...
2018: Frontiers in Cellular Neuroscience
Lei Zhu, Liang-Cui Chu, Yan Liang, Xue-Qin Zhang, Li-Qun Chen, De Ye
In flowering plants, the interaction of pollen tubes with female tissues is important for the accomplishment of double fertilization. Little is known about the mechanisms that underlie signalling between pollen tubes and female tissues. In this study, two Arabidopsis pollen tube-expressed CrRLK1L protein kinases, Buddha's Paper Seal 1 (BUPS1) and BUPS2, were identified as being required for normal tip growth of pollen tubes in the pistil. They are expressed prolifically in pollen and pollen tubes and are localized on the plasma membrane of the pollen tube tip region...
May 15, 2018: Plant Journal: for Cell and Molecular Biology
Mingyue Gou, Xiuzhi Ran, Dwight W Martin, Chang-Jun Liu
Lignin is a complex and irregular biopolymer of crosslinked phenylpropanoid units in plant secondary cell walls. Its biosynthesis requires three endoplasmic reticulum (ER)-resident cytochrome P450 monooxygenases, C4H, C3'H and F5H, to establish the structural characteristics of its monomeric precursors. These P450 enzymes were reported to associate with each other or potentially with other soluble monolignol biosynthetic enzymes to form an enzyme complex or a metabolon. However, the molecular basis governing such enzyme or pathway organization remains elusive...
May 2018: Nature Plants
Sanket Patel, Tahir Hussain
PURPOSE OF REVIEW: Angiotensin type 2 receptor (AT2 R) and receptor Mas (MasR) are part of the "protective arm" of the renin angiotensin system. Gene and pharmacological manipulation studies reveal that AT2 R and MasR are involved in natriuretic, vasodilatory, and anti-inflammatory responses and in lowering blood pressure in various animal models under normal and pathological conditions such as salt-sensitive hypertension, obesity, and diabetes. The scope of this review is to discuss co-localization and heterodimerization as potential molecular mechanisms of AT2 R- and MasR-mediated functions including antihypertensive activities...
May 1, 2018: Current Hypertension Reports
Edinson Puentes-Cala, Manuel Liebeke, Stephanie Markert, Jens Harder
The enzymatic functionalization of hydrocarbons is a central step in the global carbon cycle initiating the mineralization of methane, isoprene and monoterpenes, the most abundant biologically produced hydrocarbons. Also, terpene-modifying enzymes have found many applications in the energy-economic biotechnological production of fine chemicals. Here we describe a limonene dehydrogenase that was purified from the facultatively anaerobic betaproteobacterium Castellaniella defragrans 65Phen grown on monoterpenes under denitrifying conditions in the absence of molecular oxygen...
May 1, 2018: Journal of Biological Chemistry
A A Igolkina, Yu B Porozov, E P Chizhevskaya, E E Andronov
Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF) of Rhizobium leguminosarum bv. viciae , were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We carried out this analysis based on the hypothesis that in a contact zone of two docked components (proteins or ligands) the population polymorphism or conservatism is mutual, i...
2018: Frontiers in Plant Science
Atsuro Oishi, Erika Cecon, Ralf Jockers
The melatonin receptor subfamily is composed of three members, MT1 and MT2 , which are binding to melatonin, and GPR50, which shows high sequence homology to MT1 and MT2 but does not bind to melatonin or any other known ligand. An interesting feature of these receptors is their capacity to form homo- and heteromers between each other and also with other GPCRs. The following heteromers have been described: MT1 /MT2 , MT1 /GPR50, and heteromers composed of MT2 and the serotonin 5-HT2c receptor or the orphan GPR61, GPR62, and GPR135 receptors...
2018: International Review of Cell and Molecular Biology
Sergi Ferré, Jordi Bonaventura, Wendy Zhu, Candice Hatcher-Solis, Jaume Taura, César Quiroz, Ning-Sheng Cai, Estefanía Moreno, Verónica Casadó-Anguera, Alexxai V Kravitz, Kimberly R Thompson, Dardo G Tomasi, Gemma Navarro, Arnau Cordomí, Leonardo Pardo, Carme Lluís, Carmen W Dessauer, Nora D Volkow, Vicent Casadó, Francisco Ciruela, Diomedes E Logothetis, Daniel Zwilling
The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the direct and indirect striatal efferent pathways, respectively. With optogenetic techniques it has been possible to dissect a differential role of the direct and indirect pathways in mediating "Go" responses upon exposure to reward-related stimuli and "NoGo" responses upon exposure to non-rewarded or aversive-related stimuli, respectively, which depends on their different connecting output structures and their differential expression of dopamine and adenosine receptor subtypes...
2018: Frontiers in Pharmacology
Anna Pawełczyk, Katarzyna Sowa-Kasprzak, Dorota Olender, Lucjusz Zaprutko
The design and discovery of novel drug candidates are the initial and most probably the crucial steps in the drug development process. One of the tasks of medicinal chemistry is to produce new molecules that have a desired biological effect. However, even today the search for new pharmaceuticals is a very complicated process that is hard to rationalize. Literature provides many scientific reports on future prospects of design of potentially useful drugs. Many trends have been proposed for the design of new drugs containing different structures (dimers, heterodimers, heteromers, adducts, associates, complexes, biooligomers, dendrimers, dual-, bivalent-, multifunction drugs and codrugs, identical or non-identical twin drugs, mixed or combo drugs, supramolecular particles and various nanoindividuals...
April 6, 2018: International Journal of Molecular Sciences
Gemma Navarro, Arnau Cordomí, Verónica Casadó-Anguera, Estefanía Moreno, Ning-Sheng Cai, Antoni Cortés, Enric I Canela, Carmen W Dessauer, Vicent Casadó, Leonardo Pardo, Carme Lluís, Sergi Ferré
G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A2A receptor and dopamine D2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC...
March 28, 2018: Nature Communications
Fenghua Bao, Chang-Lin Li, Xu-Qiao Chen, Ying-Jin Lu, Lan Bao, Xu Zhang
Opioid receptors play an important role in mediating the spinal analgesia. The μ-opioid receptor (MOR) is the major target of opioid drugs widely used in clinics. However, the regulatory mechanisms of analgesic effect and tolerance for clinical MOR-targeting opioids remain to be fully investigated. Previous studies showed the interaction of δ-opioid receptor (DOR) with MOR to form the MOR/DOR heteromers that could be processed in the degradation pathway after DOR agonist treatment. Here we showed that clinical MOR-targeting opioids, morphine, fentanyl and methadone, but not tramadol, caused MOR co-internalization with DORs in both transfected human embryonic kidney 293 cells and primary sensory neurons...
January 1, 2018: Molecular Pain
C Boulard, J Thévenin, O Tranquet, V Laporte, L Lepiniec, B Dubreucq
The LAFL transcription factors LEC2, ABI3, FUS3 and LEC1 are master regulators of seed development. LEC2, ABI3 and FUS3 are closely related proteins that contain a B3-type DNA binding domain. We have previously shown that LEC1 (a NF-YB type protein) can increase LEC2 and ABI3 but not FUS3 activity. Interestingly, FUS3, LEC2 and ABI3 contain a B2 domain, the function of which remains elusive. We showed that LEC1 and LEC2 partially co-localised in the nucleus of developing embryos. By comparing protein sequences from various species, we identified within the B2 domains a set of highly conserved residues (i...
March 23, 2018: Biochimica et Biophysica Acta
Ewa Galaj, Scott Ewing, Robert Ranaldi
In the search for efficacious pharmacotherapies to treat cocaine addiction much attention has been given to agents targeting dopamine D1 or D3 receptors because of the involvement of these receptors in drug-related behaviors. D1-like and D3 receptor partial agonists and antagonists have been shown to reduce drug reward, reinstatement of drug seeking and conditioned place preference (CPP) in rodents and non-human primates. However, translation of these encouraging results to clinical settings has been limited due to a number of factors including toxicity, poor pharmacokinetic properties and extrapyramidal and sedative side effects...
March 22, 2018: Neuroscience and Biobehavioral Reviews
Yicong Cai, Sanfeng Li, Guiai Jiao, Zhonghua Sheng, Yawen Wu, Gaoneng Shao, Lihong Xie, Cheng Peng, Junfeng Xu, Shaoqing Tang, Xiangjin Wei, Peisong Hu
Starch is the main form of energy storage in higher plants. Although several enzymes and regulators of starch biosynthesis have been defined, the complete molecular machinery remains largely unknown. Screening for irregularities in endosperm formation in rice represents valuable prospect for studying starch synthesis pathway. Here, we identified a novel rice white-core endosperm and defective grain filling mutant, ospk2, which displays significantly lower grain weight, decreased starch content and alteration of starch physicochemical properties when compared to wild-type grains...
March 25, 2018: Plant Biotechnology Journal
Sonja Hinz, Gemma Navarro, Dasiel Borroto-Escuela, Benjamin F Seibt, York-Christoph Ammon, Elisabetta de Filippo, Azeem Danish, Svenja K Lacher, Barbora Červinková, Muhammad Rafehi, Kjell Fuxe, Anke C Schiedel, Rafael Franco, Christa E Müller
The adenosine receptor (AR) subtypes A2A and A2B are rhodopsin-like Gs protein-coupled receptors whose expression is highly regulated under pathological, e.g. hypoxic, ischemic and inflammatory conditions. Both receptors play important roles in inflammatory and neurodegenerative diseases, are blocked by caffeine, and have now become major drug targets in immuno-oncology. By Förster resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), bimolecular fluorescence complementation (BiFC) and proximity ligation assays (PLA) we demonstrated A2A -A2B AR heteromeric complex formation...
March 2, 2018: Oncotarget
Omar Alijevic, Hassan Hammoud, Anand Vaithia, Viktor Trendafilov, Maud Bollenbach, Martine Schmitt, Frederic Bihel, Stephan Kellenberger
Acid-sensing ion channels (ASICs) are neuronal Na+ -selective ion channels that open in response to a rapid extracellular acidification. They are involved in pain, fear, learning and neurodegeneration after ischemic stroke. 2-Guanidine-4-methylquinazoline (GMQ) was recently discovered as the first nonproton activator of ASIC3. GMQ is of interest as a gating modifier and pore blocker of ASICs. It has however a low potency, and exerts opposite effects on ASIC1a and ASIC3. To further explore the molecular mechanisms of GMQ action, we have used the guanidinium moiety of GMQ as a scaffold and tested the effects of different GMQ derivatives on the ASIC pH dependence and maximal current...
March 22, 2018: ACS Chemical Neuroscience
Nicola Montalbetti, James G Rooney, Allison L Marciszyn, Marcelo D Carattino
Acid-sensing ion channels (ASICs) are trimeric proton-activated cation selective neuronal channels that are considered to play important roles in mechanosensation and nociception. Here we investigated the role of ASIC3, a subunit primarily expressed in sensory neurons, in bladder sensory signaling and function. We found that extracellular acidification evokes a transient increase in current, consistent with the kinetics of activation and desensitization of ASICs, in ~ 25% of the bladder sensory neurons harvested from both wild type (WT) and ASIC3 knockout (KO) mice...
March 21, 2018: American Journal of Physiology. Renal Physiology
Víctor Fernandez-Duenas, Sergi Ferré, Francisco Ciruela
No abstract text is available yet for this article.
February 2018: Neural Regeneration Research
Magdalena Kolasa, Joanna Solich, Agata Faron-Górecka, Dariusz Żurawek, Paulina Pabian, Sylwia Łukasiewicz, Maciej Kuśmider, Kinga Szafran-Pilch, Marta Szlachta, Marta Dziedzicka-Wasylewska
Recently, it has been shown that serotonin 5-HT1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2)...
May 1, 2018: Neuroscience
Héctor Gaitán-Peñas, Michael Pusch, Raúl Estévez
Volume-regulated anion channels (VRACs) play a role in controlling cell volume by opening upon cell swelling. Apart from controlling cell volume, their function is important in many other physiological processes, such as transport of metabolites or drugs, and extracellular signal transduction. VRACs are formed by heteromers of the pannexin homologous protein LRRC8A (also named Swell1) with other LRRC8 members (B, C, D, and E). LRRC8 proteins are difficult to study, since they are expressed in all cells of our body, and the channel stoichiometry can be changed by overexpression, resulting in non-functional heteromers...
March 2, 2018: International Journal of Molecular Sciences
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