scholarly journals Interaction of retinal guanylate cyclase with the α subunit of transducin: potential role in transducin localization

2009 ◽  
Vol 417 (3) ◽  
pp. 803-812 ◽  
Author(s):  
Derek H. Rosenzweig ◽  
K. Saidas Nair ◽  
Konstantin Levay ◽  
Igor V. Peshenko ◽  
John W. Crabb ◽  
...  
Keyword(s):  
G Protein ◽  
Guanylate Cyclase ◽  
Potential Role ◽  
Bright Light ◽  
Α Subunit ◽  
Protein Protein Interaction ◽  
Rod Cells ◽  
G Protein Signalling ◽  
Cgmp Synthesis ◽  
Kinase Homology Domain

Vertebrate phototransduction is mediated by cGMP, which is generated by retGC (retinal guanylate cyclase) and degraded by cGMP phosphodiesterase. Light stimulates cGMP hydrolysis via the G-protein transducin, which directly binds to and activates phosphodiesterase. Bright light also causes relocalization of transducin from the OS (outer segments) of the rod cells to the inner compartments. In the present study, we show experimental evidence for a previously unknown interaction between Gαt (the transducin α subunit) and retGC. Gαt co-immunoprecipitates with retGC from the retina or from co-transfected COS-7 cells. The retGC–Gαt complex is also present in cones. The interaction also occurs in mice lacking RGS9 (regulator of G-protein signalling 9), a protein previously shown to associate with both Gαt and retGC. The Gαt–retGC interaction is mediated primarily by the kinase homology domain of retGC, which binds GDP-bound Gαt stronger than the GTP[S] (GTPγS; guanosine 5′-[γ-thio]triphosphate) form. Neither Gαt nor Gβγ affect retGC-mediated cGMP synthesis, regardless of the presence of GCAP (guanylate cyclase activating protein) and Ca2+. The rate of light-dependent transducin redistribution from the OS to the inner segments is markedly accelerated in the retGC-1-knockout mice, while the migration of transducin to the OS after the onset of darkness is delayed. Supplementation of permeabilized photoreceptors with cGMP does not affect transducin translocation. Taken together, these results suggest that the protein–protein interaction between Gαt and retGC represents a novel mechanism regulating light-dependent translocation of transducin in rod photoreceptors.

scholarly journals RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of Gαo

2000 ◽  
Vol 350 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Sabine TRAVER ◽  
Carole BIDOT ◽  
Nathalie SPASSKY ◽  
Tania BALTAUSS ◽  
Marie-France DE TAND ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
G Protein ◽  
Rgs Proteins ◽  
Gtpase Activity ◽  
Α Subunit ◽  
Adult Mice ◽  
G Protein Signalling ◽  
Marked Preference

In an attempt to elucidate the physiological function(s) of the Ras-related Rap proteins, we used the yeast two-hybrid system and isolated a cDNA encoding a protein that interacts with both Rap1 and Rap2, but not with Ras; the use of Rap2 mutants showed that this interaction is characteristic of a potential Rap effector. This protein was identified as RGS14, a member of the recently discovered family of RGS (‘regulators of G-protein signalling’) proteins that stimulate the GTPase activity of the GTP-binding α subunit of heterotrimeric G-proteins (Gα). Deletion analysis, as well as in vitro binding experiments, revealed that RGS14 binds Rap proteins through a domain distinct from that carrying the RGS identity, and that this domain shares sequence identity with the Ras/Rap binding domain of B-Raf and Raf-1 kinases. RGS14 is distinguished from other RGS proteins by its marked preference for Gαo over other Gα subunits: RGS14 binds preferentially to Gαo in isolated brain membranes, and also interacts preferentially with Gαo (as compared with Gαi1) to stimulate its GTPase activity. In adult mice, RGS14 expression is restricted to spleen and brain. In situ hybridization studies showed that it is highly expressed only in certain areas of mouse brain (such as the CA1 and CA2 regions of the hippocampus), and that this pattern closely resembles that of Rap2, but not Rap1, expression. Double in situ hybridization experiments revealed that certain cells in the hippocampus express both RGS14 and Gαo, as well as both RGS14 and Rap2, showing that the interaction of RGS14 with Gαo and Rap2 is physiologically possible. Taken together, these results suggest that RGS14 could constitute a bridging molecule that allows cross-regulation of signalling pathways downstream from G-protein-coupled receptors involving heterotrimeric proteins of the Gi/o family and those involving the Ras-related GTPase Rap2.

Knockdown of regulator of G-protein signalling 2 (Rgs2) leads to abnormal early mouse embryo development in vitro

2015 ◽  
Vol 27 (3) ◽  
pp. 557 ◽  
Author(s):  
Yan Zhu ◽  
Ya-Hong Jiang ◽  
Ya-Ping He ◽  
Xuan Zhang ◽  
Zhao-Gui Sun ◽  
...  
Keyword(s):  
Embryonic Development ◽  
G Protein ◽  
Embryo Development ◽  
Expression Patterns ◽  
Critical Role ◽  
Α Subunit ◽  
G Protein Signalling ◽  
Early Embryos ◽  
Development In Vitro

Regulator of G-protein signalling 2 (Rgs2) is involved in G-protein-mediated signalling by negatively regulating the activity of the G-protein α-subunit. In the present study, the expression patterns of Rgs2 in mouse ovarian tissues and early embryos were determined by semiquantitative reverse transcription–polymerase chain reaction, immunohistochemistry and immunofluorescent analyses. Rgs2 expression was observed in the ovarian tissues of adult female mice, with an almost equal expression levels during different stages of the oestrous cycle. Rgs2 was abundant in the cytoplasm, membrane, nuclei and spindles of intact polar bodies in mouse early embryos at different developmental stages from the zygote to blastocyst. The effect of Rgs2 knockdown on early embryonic development in vitro was examined by microinjecting Rgs2-specific short interfering (si) RNAs into mouse zygotes. Knockdown of endogenous Rgs2 expression led to abnormal embryonic development in vitro, with a considerable number of early embryos arrested at the 2- or 4-cell stage. Moreover, mRNA expression of three zygotic gene activation-related genes (i.e. Zscan4, Tcstv1 and MuERV-L) was decreased significantly in 2-cell arrested embryos. These results suggest that Rgs2 plays a critical role in early embryo development.

The regulator of G-protein signalling protein mediates D-glucose-induced stomatal closure via triggering hydrogen peroxide and nitric oxide production in Arabidopsis

2018 ◽  
Vol 45 (5) ◽  
pp. 509 ◽  
Author(s):  
Shumei Hei ◽  
Zhifeng Liu ◽  
Aixia Huang ◽  
Xiaoping She
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
G Protein ◽  
Stomatal Closure ◽  
H2o2 Production ◽  
No Production ◽  
Α Subunit ◽  
G Protein Signalling ◽  
Guanine Nucleotide Binding ◽  
Nucleotide Binding Proteins

2-Deoxy-D-glucose, 3-O-methyl-D-glucose and D-mannose are all non-metabolisable D-glucose analogues. Among these, 2-deoxy-D-glucose and D-mannose are substrates for hexokinase (HXK). D-sorbitol and D-mannitol are reduced forms of D-glucose and are typically used as comparable osmotic solutes. Similar to 2-deoxy-D-glucose and D-mannose, D-glucose induced stomatal closure in Arabidopsis, whereas 3-O-methyl-D-glucose, D-sorbitol and D-mannitol did not. The data show that the effect of D-glucose on stomata is metabolism-independent, HXK-dependent and irrelevant to osmotic stress. Additionally, the D-glucose induced closure of stomata in wild-type Arabidopsis, but did not in rgs1-1 and rgs1-2 or gpa1-3 and gpa1-4 mutants, indicating that the regulator of G-protein signalling protein (RGS1) and heterotrimeric guanine nucleotide-binding proteins (G proteins)-α subunit (Gα) also mediate the stomatal closure triggered by D-glucose. Furthermore, the effects of D-glucose on hydrogen peroxide (H2O2) or nitric oxide (NO) production and stomatal closure were more significant in AtrbohD or Nia2-1 mutants than in AtrbohF and AtrbohD/F or Nia1-2 and Nia2-5/Nia1-2. The data indicate that H2O2 sourced from AtrbohF and NO generated by Nia1 are essential for D-glucose-mediated stomatal closure. D-glucose-induced H2O2 and NO production in guard cells were completely abolished in rgs1-1 and rgs1-2, which suggests that RGS1 stimulates H2O2 and NO production in D-glucose-induced stomatal closure. Collectively, our data reveal that both HXK and RGS1 are required for D-glucose-mediated stomatal closure. In this context, D-glucose can be sensed by its receptor RGS1, thereby inducing AtrbohF-dependent H2O2 production and Nia1-catalysed NO accumulation, which in turn stimulates stomatal closure.

scholarly journals Heterotrimeric G-protein α subunit (RGA1) regulates tiller development, yield, cell wall, nitrogen response and biotic stress in rice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ravi Ramesh Pathak ◽  
Vikas Kumar Mandal ◽  
Annie Prasanna Jangam ◽  
Narendra Sharma ◽  
Bhumika Madan ◽  
...  
Keyword(s):  
Cell Wall ◽  
Network Analysis ◽  
G Protein ◽  
Heading Date ◽  
Ppi Network ◽  
Nitrogen Response ◽  
Α Subunit ◽  
Protein Protein Interaction ◽  
G Protein Alpha Subunit ◽  
Agronomically Important Traits

AbstractG-proteins are implicated in plant productivity, but their genome-wide roles in regulating agronomically important traits remain uncharacterized. Transcriptomic analyses of rice G-protein alpha subunit mutant (rga1) revealed 2270 differentially expressed genes (DEGs) including those involved in C/N and lipid metabolism, cell wall, hormones and stress. Many DEGs were associated with root, leaf, culm, inflorescence, panicle, grain yield and heading date. The mutant performed better in total weight of filled grains, ratio of filled to unfilled grains and tillers per plant. Protein–protein interaction (PPI) network analysis using experimentally validated interactors revealed many RGA1-responsive genes involved in tiller development. qPCR validated the differential expression of genes involved in strigolactone-mediated tiller formation and grain development. Further, the mutant growth and biomass were unaffected by submergence indicating its role in submergence response. Transcription factor network analysis revealed the importance of RGA1 in nitrogen signaling with DEGs such as Nin-like, WRKY, NAC, bHLH families, nitrite reductase, glutamine synthetase, OsCIPK23 and urea transporter. Sub-clustering of DEGs-associated PPI network revealed that RGA1 regulates metabolism, stress and gene regulation among others. Predicted rice G-protein networks mapped DEGs and revealed potential effectors. Thus, this study expands the roles of RGA1 to agronomically important traits and reveals their underlying processes.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

scholarly journals Genetic Involvement of a cAMP-Dependent Protein Kinase in a G Protein Signaling Pathway Regulating Morphological and Chemical Transitions in Aspergillus nidulans

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 591-600
Author(s):  
Kiminori Shimizu ◽  
Nancy P Keller
Keyword(s):  
Protein Kinase ◽  
Aspergillus Nidulans ◽  
Signaling Pathway ◽  
G Protein ◽  
Radial Growth ◽  
Morphological Development ◽  
Dependent Protein Kinase ◽  
Α Subunit ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein

Abstract In the filamentous fungus Aspergillus nidulans, a heterotrimeric G protein α-subunit and an RGS domain protein, encoded by fadA and flbA, respectively, regulate production of the carcinogenic metabolite sterigmatocystin (ST) and asexual spores (i.e., conidia). We investigated the genetic involvement of the cAMP-dependent protein kinase catalytic subunit (PkaA), a potential downstream target of FadA activity, in ST production and conidiation. Relative to wild type, sporulation was decreased in the pkaA overexpression strain but was not totally absent, as occurs in ΔflbA or fadAG42R (fadA-dominant active) strains. Deletion of pkaA resulted in a hyper-conidiating strain with limited radial growth. This phenotype was epistatic to mutation in flbA or fadA; the double mutants ΔpkaA; ΔflbA and ΔpkaA; fadAG42R recovered sporulation and their radial growth was severely restricted. PkaA overexpression also negatively regulated AflR, the ST biosynthesis-specific transcription factor, both transcriptionally and post-transcriptionally. Deletion of pkaA restored ST production in the ΔflbA background but not in the fadAG42R background. These data provide genetic evidence that the FlbA/FadA signaling pathway regulating ST production and morphological development is partially mediated through PkaA.

scholarly journals RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serina Yokoyama ◽  
Tatsuo Kawai ◽  
Koichi Yamamoto ◽  
Huang Yibin ◽  
Hiroko Yamamoto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Epithelial Cells ◽  
G Protein ◽  
Rat Kidney ◽  
Chinese Hamster ◽  
Cellular Responses ◽  
Type I ◽  
Α Subunit ◽  
Mesenchymal Transition

AbstractThe receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands. We generated Chinese hamster ovary (CHO) cells stably expressing RAGE and AT1, mutated AT1, or AT2 receptor. The activation of two types of G protein α-subunit, Gq and Gi, was estimated through the accumulation of inositol monophosphate and the inhibition of forskolin-induced cAMP production, respectively. Rat kidney epithelial cells were used to assess RAGE ligand-induced cellular responses. We determined that RAGE ligands activated Gi, but not Gq, only in cells expressing RAGE and wildtype AT1. The activation was inhibited by an AT1 blocker (ARB) as well as a RAGE inhibitor. ARBs inhibited RAGE ligand-induced ERK phosphorylation, NF-κB activation, and epithelial–mesenchymal transition of rat renal epithelial cells. Our findings suggest that the activation of AT1 plays a central role in RAGE-mediated cellular responses and elucidate the role of a novel molecular mechanism in the development of cardiovascular diseases.

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