Goprotein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway

Moriarty, Thomas; Padrell, Elena; Carty, D. J.; Omri, Gila; Landau, Emmanuel M.; Iyengar, Ravi

doi:10.1038/343079a0

Cited by 186 publications

(65 citation statements)

References 23 publications

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“…Although the G proteins that release the activating ␤␥ subunits are not identified, there is evidence, that they are subtypes of the pertussis toxin-sensitive G i /G o family (33). The involvement of G o proteins in phospholipase C regulation was first observed in experiments on Xenopus oocytes demonstrating that G o proteins specifically enhance the Cl Ϫ current elicited by muscarinic receptors via IP 3 and Ca 2ϩ (42)(43)(44). The observation that olfactory phospholipase C activation occurs through ␤␥ subunits of a G o -like G protein is thus of particular interest and in line with previous studies indicating that odorant-induced IP 3 formation in rat olfactory cilia is mediated by a pertussis toxinsensitive G protein (5).…”

Section: Discussionmentioning

confidence: 99%

Odorants Selectively Activate Distinct G Protein Subtypes in Olfactory Cilia

Schandar

Laugwitz

Boekhoff

et al. 1998

Journal of Biological Chemistry

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Chemoelectrical signal transduction in olfactory neurons appears to involve intracellular reaction cascades mediated by heterotrimeric GTP-binding proteins. In this study attempts were made to identify the G protein subtype(s) in olfactory cilia that are activated by the primary (odorant) signal. Antibodies directed against the ␣ subunits of distinct G protein subtypes interfered specifically with second messenger reponses elicited by defined subsets of odorants; odor-induced cAMP-formation was attenuated by G␣ s antibodies, whereas G␣ o antibodies blocked odor-induced inositol 1,4,5-trisphosphate (IP 3 ) formation. Activation-dependent photolabeling of G␣ subunits with [␣- Chemoelectrical signal transduction is considered to be mediated via intracellular reaction cascades triggered by G protein-coupled receptors (1). Biochemical studies over the last decade have revealed that odorants elicit the formation of either cAMP or IP 3 1 in olfactory preparations (2-6). Whereas the functional implications of the dual transduction pathways in the crustacean olfactory system are well established (7,8), in vertebrates the relative importance of the two pathways in olfactory signaling remains controversial (9, 10). Heterotrimeric GTP-binding proteins play a key role in signal transduction processes, coupling activated receptors to the appropriate effector system. A variety of different G␣ subtypes have been identified in vertebrate olfactory epithelium including G s short , G il , G i2 , G i3 , G o , and G q (11-17). Even an olfactory-specific isoform of G s (G olf ) has been discovered (18). However, it is currently unclear how many and which type of G proteins are involved in olfactory signal transduction. To approach the question of which G protein subtype(s) may mediate the transduction processes in olfactory sensory cells, it is necessary to identify the G protein that is activated upon stimulation with distinct odor ligands. This can be accomplished by an activationdependent labeling procedure (19), in which receptor-activated G protein ␣ subunits are photolabeled using the hydrolysisresistant GTP-analogue [␣-32 P]GTP azidoanilide. Subsequent immunoprecipitation of G␣ subunits with subtype-specific antibodies permits identification of G protein subtypes that are labeled upon stimulation of olfactory cilia preparations with distinct odorants. The data indicate that cAMP-and IP 3 -inducing odorants result in labeling of different G protein subtypes. EXPERIMENTAL PROCEDURES MaterialsSprague-Dawley rats were purchased from Charles River, Sulzfeld. The odorants citralva (3,7-dimethyl-2,6-octadiennitrile), hedione (3-oxo-2-pentyl cyclopentaneacetic acid methyl ester), eugenol (2-methoxy-4-(2-propenyl)phenol), lilial (para-butyl-␣-methyl hydrocinnamic aldehyde), lyral (4-(4-hydroxy-4-methyl pentyl)-3-cyclohexene-10-carboxyldehyde), and ethylvanillin (3-ethoxy-4-hydroxybenzaldehyde) were provided by DROM, Baierbrunn. Isovaleric acid (3-methylbutanoic acid) and pyrrolidine (tetrahydropyrrole) were purchased from Sigma. The ra...

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Section: Discussionmentioning

confidence: 99%

Odorants Selectively Activate Distinct G Protein Subtypes in Olfactory Cilia

Schandar

Laugwitz

Boekhoff

et al. 1998

Journal of Biological Chemistry

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“…Thus, a small amount of residual G, remaining after antisense depletion was sufficient to couple GRP-R but not NMB-R. Alternatively, the GRP-R may use neither G,, nor G,,, for coupling. Moriarty et al [30] and Blitzer et al [31], using microinjection of the purified protein subunits into Xenopus oocytes, have proposed that G, mediates responses to serotonin and &,B-adrenergic receptors expressed in oocytes. Their conclusions were supported by an antisense experiment, in which oocytes were assayed 24 h after its injection.…”

Section: -mentioning

confidence: 99%

Neuromedin B receptor, expressed in Xenopus laevis oocytes, selectively couples to G_αq and not G_α11

et al. 1994

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G-proteins of the q family have been implicated as mediators of bombesin receptors action. We cloned Xenopus G, and G,,, and specifically disrupted the synthesis of either protein with selective antisense oligonucleotides. CC14 antisense inhibited responses mediated by neuromedin B receptor (NMB-R) by 74%, though not by gastrin-releasing peptide receptor (GRP-R). G,,, antisense had little effect on either GRP-R-or NMB-R-mediated responses. This suggests that NMB-R couples to G,_, and that GRP-R and NMB-R show distinct G-protein coupling preferences in the Xenopus oocyte.

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“…The G proteins that regulate polyphosphoinositide-specific phospholipase C are particularly elusive, with evidence for regulation by both pertussis toxin-sensitive and -insensitive G proteins (Taylor & Merritt, 1986;Harden, 1989). In Xenopus oocytes activated ao appears to stimulate the enzyme (Moriarty et al, 1990) and less direct evidence from other tissues is consistent with stimulation by the a subunits of unidentified G proteins (Boyer et al, 1989). Earlier claims that the p21 ras proteins are the G proteins that couple receptors to polyphosphoinositide-specific phospholipase C have now been refuted (Downward et al, 1988).…”

Section: G Proteins and Effector Systemsmentioning

confidence: 84%

The role of G proteins in transmembrane signalling

Taylor

1990

Biochemical Journal

226

113

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INTRODUCTIONIn some transmembrane signalling systems detection of the extracellular stimulus and generation of an intracellular response are properties of the same protein or protein complex. Binding of acetylcholine to the a subunits of the pentameric nicotinic receptor, for example, opens a cation-selective channel formed by parts of each of the receptor subunits, and insulin when it binds to the extracellular domain of its receptor activates a protein tyrosine kinase activity in the intracellular domain of the same protein. Rodbell and his collaborators (Rodbell et al., 1971) were the first to provide evidence for a more complex class of signalling pathway where the sensor and intracellular effector are separate proteins that communicate through a guanine nucleotide-dependent regulatory protein or G protein. The G protein cycles between inactive GDP-bound and active GTPbound forms. Activation is catalysed by receptors and deactivation is an intrinsic property of the G protein, its GTPase activity. The developments that followed Rodbell's pioneering studies have established that many different receptors regulate many intracellular effectors through a family of closely related G proteins (Citri & Schramm, 1980;Rodbell, 1980;Schramm & Selinger, 1984;Northup, 1985;Levitzki, 1988). Many excellent recent reviews have focused on various aspects of these interactions between receptors, G proteins and intracellular effectors (Casperson & Bourne, 1987;Gilman, 1987;Allende, 1988;Lochrie & Simon, 1988;Weiss et al., 1988;Chabre & Deterre, 1989;Ross, 1989;Houslay, 1990).The G protein cycle, at the centre of the conversation between receptors and their effectors, provides one solution to the compromise that cells must make between responding rapidly and being able to respond to very low concentrations of extracellular stimulus. In this review I will consider how different signalling mechanisms are adapted to the cellular processes they control by comparing the properties of the signalling pathways that involve G proteins with the simpler pathways that do not.

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Goprotein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway

Cited by 186 publications

References 23 publications

Odorants Selectively Activate Distinct G Protein Subtypes in Olfactory Cilia

Odorants Selectively Activate Distinct G Protein Subtypes in Olfactory Cilia

Neuromedin B receptor, expressed in Xenopus laevis oocytes, selectively couples to G_αq and not G_α11

The role of G proteins in transmembrane signalling

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Goprotein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway

Cited by 186 publications

References 23 publications

Odorants Selectively Activate Distinct G Protein Subtypes in Olfactory Cilia

Odorants Selectively Activate Distinct G Protein Subtypes in Olfactory Cilia

Neuromedin B receptor, expressed in Xenopus laevis oocytes, selectively couples to Gαq and not Gα11

The role of G proteins in transmembrane signalling

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Neuromedin B receptor, expressed in Xenopus laevis oocytes, selectively couples to G_αq and not G_α11