GNAO1

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..specifically with members of the G alpha i subfamily, G alpha i1, G alpha i2, G alpha i3, G alpha z, and G alpha o, but not with members of other G alpha subfamilies, G alpha s, G alpha q, and G alpha 12/13...

..35S]GTP gamma S binding, mu-agonist-induced adenylyl cyclase inhibition, and co-precipitation of G alpha o, G alpha i2 G alpha z and G alpha q11 subunits with mu-opioid receptors...

..These findings support a role for the M1 receptor subtype as the primary G(alpha)(q)/11-coupled muscarinic receptor in mouse hippocampus and cortex...

..a sensory neuron subfamily characterized by the expression of the G-protein Galpha(o) subunit (also known as Gnao) and Vmn2r putative pheromone receptors (V2Rs)...

..3-q32) and the human guanine nucleotide-binding regulatory protein Go-alpha (GNAO1 localized at 16q13) was significantly decreased in individuals with schizophrenia compared to unaffected family ..

..Both of these mechanisms could be involved in the neuroprotective signalling of oestrogens that contributes to their preventive/therapeutic action against postmenopausal neurological disorders...

..Our observations indicate that pheromones in male urine act on vomeronasal neurons in the female VNO via a receptor-mediated, G alpha(q/11)-protein-dependent increase in IP(3) levels...

..showed that the level of G alpha s mRNA was increased in the septum and brainstem, and the level of G alpha o mRNA was elevated in the cortex during the pentobarbital withdrawal...

..Furthermore, the exchange of a few carboxyl-terminal residues of G alpha q by those of G alpha 12 or G alpha o allows the resulting chimeric G alpha subunits (G alpha ql and G alpha qol respectively) to couple Gi-coupled ..

..The results show that the endogenous octopamine system in C. elegans is activated by starvation and that different environmental stimuli can activate CREB through G alpha(q)...

..The canonical WNT-beta-catenin signaling pathway requires both G alpha o and G alpha q heterotrimeric G-proteins, whereas we show that WNT-JNK signaling requires only G alpha o protein...

..These studies demonstrate that PAR1 and PAR2 physically and functionally link to overlapping and distinct profiles of G proteins to differentially regulate downstream signaling pathways and cell physiology...

..To investigate the role of G alpha o in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of G ..

..Given the presence of formylated peptides in bacteria and mitochondria, possible roles for VNO FPRs include the assessment of conspecifics or other species based on variations in normal bacterial flora or mitochondrial proteins...

..The purpose of this study was to better define the role of these proteins by examining their expression in the rat vestibular periphery and characterizing their chromosomal location...

..This property of RGS8 may be crucial for the rapid regulation of neuronal excitability upon stimulation of G-protein-coupled receptors...

..In rodents, signal transduction pathways involve G alpha olf and G alpha i2/G alpha o in OE and VNE, respectively. Reeve's turtles (Geoclemys reevesii) live in a semiaquatic environment...

..Gbeta1, 2, and 5 are expressed in partially overlapping subpopulations of cone bipolar cells. Ggamma13 and Gbeta3 and/or Gbeta4, thus, seem selectively to participate in signal transduction by ON bipolar cells...

..long-term administration of a wide spectrum of antidepressant drugs regulate G alpha s, G alpha i1, G alpha i2, G alpha o, G alpha q, and G alpha 12 mRNA and protein expression in various areas of the rat brain...

..antisera raised against alpha and beta subunits (anti-G alpha common, anti-G beta, anti-G alpha i1/2/3, and anti-G alpha o) were used. Anti-G alpha common totally blocked the effects of NE on membrane potential and K ATP channels...

..Specifically, G alpha i2, G alpha i3, G alpha o, G alpha s, and G alpha q/11 levels reached 87%, 81%, 91%, 99%, and 103% respectively of those from normal ..

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..The decreases in D2 receptor function were unrelated to the coupled G-proteins, since none of the G alpha i-3, G alpha o or G alpha q in the ventral striatum exhibited quantitative differences between control and amphetamine ..

..by ORNs, whereas two vomeronasal receptor families (V1rs and V2rs) coupled respectively to G alpha i2 and G alpha o, are expressed by VRNs. Previously, we reported that one goat V1rs (gV1ra1) is expressed by ORNs and VRNs...

..2. Antibodies specific for G alpha q/11, but not those for G alpha o, reduced M-current inhibition by the muscarinic agonist oxotremorine-M, whereas anti-G alpha o antibodies, but ..

..Our study further demonstrates that this effect of cholesterol is due, in part, to its involvement in the interactions between AQP-6, vH(+)-ATPase and the GTP-binding G(alpha o) protein at the synaptic vesicle membrane...

..These results serve to define a novel trafficking pathway for Src family proteins that are regulated by dual fatty acylation...

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..Active forms of exogenous G protein subunits (G alpha i-1, G alpha i-2, or G alpha o) activated only KATP channels closed by ATPi...

..Overall, this study demonstrated that G alpha(o/i)-coupled CB1R triggers neurite outgrowth in Neuro-2A through the activation of a signaling network containing two pathways that bifurcate at Src and converge at Stat3...

..Thus, the G(alpha)o/i-coupled cannabinoid receptor, by regulating the proteasomal degradation of Rap1GAPII, activates Rap1 to induce neurite outgrowth...

..i2 was investigated in plasma membranes from different tissues and cells and compared to the distribution of G alpha o and other pertussis toxin sensitive G alpha...

..The most salient candidate gene within this QTL, Gnao1 (guanine nucleotide binding protein, alpha(o); G alpha(o); 96...

..In addition to a clone coding for a G alpha o-type subunit previously reported [(1989) FEBS Lett...

..Furthermore, no significant changes were observed in the levels of alpha o or alpha s isoforms following NGF removal. These findings suggest that alpha o isoforms are involved in neuritic extension in PC12 cells...

..b>G alpha o physically binds Axin and re-localizes it to the plasma membrane...

..In contrast, ferrous ligand-bound Ngb under normoxia did not have GDI activities. Taken together, we propose that human Ngb may be a novel oxidative stress-responsive sensor for signal transduction in the brain...

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..Tail tap of dauers stimulates pumping through a mechanism involving G alpha o and G alpha q...

..GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations...

..This new pathway for controlling Kir3 signaling could help limit the potential harmful effects of excessive Kir3 activity in the brain...

..We conclude that the N-terminal region directs inhibition of G(alpha) signaling by forming a complex with the GGL/RGS region and affecting its stability, membrane localization, and G(alpha) target specificity...

..Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 (a Galpha subunit) and mutant MAP2K4 (a member of the JNK signalling pathway) in oncogenesis...

..Here, we show that the N-terminus of G alpha o is critical for the interaction with the C-terminus of the P/Q-type channel subunit, and that the binding ..

..Recently the first somatic mutation, arginine(243) → histidine (R243H) in the GNAO1 (Gαo) gene was identified in breast carcinomas and shown to promote oncogenic transformation when introduced into ..

..We conclude that the G(o) proteins play a role in thrombin signaling distinct from G(i1/2) proteins, which are mediated through their Gbetagamma subunits and involve coupling to calcium signaling and cytoskeletal rearrangements...

..These data indicate that the alpha(2) AR ligand RX 831003 behaves as a protean agonist at the alpha(2A) AR and that its activity is highly dependent on the co-expressed G(alpha) protein subunit...

..This represents one mechanism by which cells route stimuli directed to multifunctional receptors to selected effectors so as to attain finely targeted signaling...

..This study suggests that one of the functions of Goalpha in the brain is to mediate extracellular signal-regulated kinase activation by G protein-coupled receptors...

..These results indicate that both CKbeta8 and CKbeta8-1 are involved in cell proliferation by modulating the cell cycle regulators...

..In light of previous reports, expression levels of the following genes: APOBEC3B, CXCL1, DRD2, GNAO1, Kir2...

..These observations suggest that G(o/i)-coupled receptors, by stimulating the degradation of RGS20, can regulate how subsequent activation of the G(s) and G(i) pathways controls cellular cAMP levels, thus allowing for signal integration...

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..RGS8 binds specifically to G alpha o and G alpha i3 in vitro and activates their intrinsic GTPase activities...

..We propose that MSP-dependent microtubule reorganization promotes meiotic spindle assembly by facilitating the search and capture of microtubules by meiotic chromatin following NEBD...

..These data provide the first direct observation of R*-mediated conformational changes in G proteins and define the structural basis for GDP release from G alpha...

..Our results reveal a tripartite organization of the VNO and AOB, question the generality of the requirement of these nine H2-Mv molecules for V2R surface expression, and suggest that H2-Mvs can function in both dendrites and axons...

..Taken together, these data imply that HDAC5 and possibly other class II HDACs can be added to the growing list of G betagamma effectors...

..We have used gene targeting to examine the role of the G protein Gαo, encoded by the gene Gnao1, in vomeronasal function...

..These results suggest that the deactivation of mGluR6 cascade during the light response may require the contribution of multiple GTPase activating proteins...

..Our results appear to link RIC-8 (synembryn) and a third major G alpha pathway, the G alpha(s) pathway, with the previously discovered G alpha(o) and G alpha(q) pathways of the synaptic signaling network...

..All the 5-HT(1) receptor types actually interact with G alpha i/G alpha o proteins to inhibit adenylyl cyclase and modulate ionic effectors, i.e. potassium and/or calcium channels...

..The aim of this study was to investigate the genome-wide transcriptional profiling of the septal wall of the RVOT in patients with RVOT tachycardia and control subjects...

..This study provides for the first time a skin-derived cellular model to analyze the molecular mechanism of the MCH signaling pathway...

..transcription of beta-actin, sema 3F, CRMP 1 to 4, GAP-43, G alpha o1, G alpha o2 and translation of beta-actin, G alpha o, G alpha o1, CRMP-2, CRMP-4 genes were examined in the hippocampus of neonatal methimazole induced hypothyroid ..

..Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling...

..Immunoblot analysis of the endogenous G-proteins revealed that Sf9 cells lack the G-protein subtypes G(alpha i 1-3) and G(alpha)o, but express the subtype G(alpha)s and G(alpha)q...

Postnatal development of G alpha o isoforms in rat cerebral cortex was studied by SDS-PAGE and immunoblotting...

..Furthermore, antisera directed against G alpha s or G alpha q but not G alpha i, G alpha o, or G alpha z precipitated specific D1-like binding sites labeled with [3H]SCH23390...

..The biological significance of Go alpha is unclear in normal and neoplastic lung tissues, but Go alpha is a useful marker of neuroendocrine cells and neoplasma of the lung...

..Substitution of the SH4 motif within Fyn with heterologous sequences from other palmitoylated proteins (G alpha o and GAP43) revealed that the presence of palmitate is sufficient to direct plasma membrane localization ..

..However, a dramatically different structure for VRs and the existence of variant VR mRNA forms indicate that there are diverse strategies to detect functionally distinct sensory stimuli...

..A detailed understanding of G alpha-membrane interactions may reveal unique mechanisms for regulating signal transduction...

..ventricular membranes, specific [3H]DPCPX binding sites were detected in immunoprecipitates of G alpha i3 and G alpha o antisera but not with antibodies for other G alpha proteins...

..we analyzed the patterns of expression of nine G protein alpha subunit mRNAs (G alpha s, G alpha i, G alpha q, G alpha o, and G alpha 11-15) in oocytes, eggs, and preimplantation embryos from fertilization to the blastocyst stage...

..Repeated WD motifs in beta form a circularized sevenfold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade...

..Deletion of this region diminishes the ability of alpha o to interact with the beta gamma subunit, but substitutions at this position indicate that other amino acids can be tolerated without affecting subunit interaction...

..at concentrations where there were no effects of other antibodies specifically directed against Gi alpha 3 or G alpha o. These data suggest that Gi1 and/or Gi2 interact with the galanin receptor and probably mediate the effects of ..

..There is 100% identity at the amino acid level for the cholera and pertussis toxin-catalyzed ADP ribosylation sites, the putative guanine nucleotide binding, and the GTP hydrolysis sites...

..This may be a mechanism by which calcium channels can normally act to limit the duration of a G-protein modulatory signal...

..The alpha subunit genes identified are: G alpha i1-3 and G alpha z but not G alpha o from the Gi family, G alpha s from the Gs family, G alpha 11, G alpha q, and G alpha 16 from the Gq family, and ..

..In the present study, we have conducted experiments to examine whether the G alpha subunit is also associated with mitotic spindles...

..This is the first report that characterizes G-protein subunits in human glomeruli. Further study is required to determine the roles of G-proteins in signal transductions in human glomeruli...

..significantly increased alpha s amounts in the hypothalamus (70%), and produced a minor elevation (30%) in G alpha o levels in the olfactory area...

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..The antiproliferative effect, like S1P-mediated ERK1/2 inhibition, was orthovanadate-sensitive and pertussis toxin-insensitive. Our results indicate that EDG-8, a member of the EDG-1 subfamily, couples to unique signaling pathways...

..We conclude that G alpha(i) and G alpha(o) are critical targets of oxidative stress for activation of ERK...

..Finally, we characterized the structure of the PLC beta 1 locus and confirmed its mapping to human chromosome 20...

..We conclude that Nef interacts with nonpalmitoylated G(o)alpha, presumably outside caveolin-rich microdomains of the plasma membrane...

..Ric-8A interacts with GDP-bound Galpha proteins, stimulates release of GDP, and forms a stable nucleotide-free transition state complex with the Galpha protein; this complex dissociates upon binding of GTP to Galpha...

..These features provide for a kinetic proofreading mechanism that sustains the fidelity of receptor-G protein coupling...

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..These findings define a novel nucleotide exchange function for Pcp2 and suggest that the interaction between Pcp2 and Galphao is important to Purkinje cell function...

..These findings support a possible involvement of VGSC in depolarization-induced activation of Go-proteins...

..As revealed by immunostaining, latrophilin interacts with G alpha q/11 and G alpha o but not with G alpha s, G alpha i or G alpha z, indicating that this receptor may couple to several G proteins ..

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..This report indicates the utility of R-G cotransfection in mammalian cells as a "natural environment model" to characterize events occurring at the R-G and G-E interface...

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..The use of oligonucleotide probes of the type described here represents a new strategy, potentially widely applicable for mapping and elucidating structural features of genes...

..The ultimate goal is to define their potential as therapeutic targets in heart disease, obesity, and diabetes. ..

..3. We will use fly genetics to determine whether G-alpha-o also transduces the Wg signal, and also identify its molecular partners in the trimeric complex. ..

..The potential use of biomarkers in lymphocytes will provide clinical researchers a tool to better address questions concerning diagnostic subgroups and treatment responders and non-responders. ..

..We believe that we are uniquely poised to study these novel mechanisms of regulation of NHE- 1, and are enthusiastic about the prospects of continuing these studies. ..

..Our aim is to produce outstanding investigators with a broad insight into glomerular dysfunction, and who will make significant contributions to the understanding of progressive glomerular disorders. ..

..The work could lead to new therapies for hypertension, congestive heart failure, cardiomyopathies and kidney failure. ..

..By understanding the accumulation of mitochondrial DNA defects in brain, it will advance mitochondrial medicine for earlier diagnosis and treatment of brain related disorders. ..

..The work could lead to new therapies for hypertension, congestive heart failure, cardiomyopathies and kidney failure. ..

..Our aim is to produce outstanding investigators with a broad insight into glomerular dysfunction, and who will make significant contributions to the understanding of progressive glomerular disorders. ..

..This proposal could also lay the foundation for future structural experiments utilizing NMR and/or crystallography methods. ..

..These studies address important gaps in our knowledge of GPCR signals that regulate the functions of RTK's. ..

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..Total project cost is $4,212,617, of which the University's share is 53 percent. ..

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..The total project cost is $6,342,887; the University is contributing $3,171,443 (50 percent). ..

..Number 2. To establish a role for ROS generated by NAD(P)H oxidase in an animal model of proliferative and fibrotic renal disease. ..

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