G Protein Pathways

Neves, Susana R.; Ram, Prahlad T.; Iyengar, Ravi

doi:10.1126/science.1071550

Cited by 1,120 publications

(969 citation statements)

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“…GRs are putative GPCRs, suggesting that chemosensory detection utilizes a typical GPCR signaling pathway. Upon binding of an extracellular ligand, a GPCR activates the intracellular G-protein consisting of an αβγ heterotrimer bound to GDP [78,79]. The α subunit exchanges GDP for GTP and Fig.…”

Section: Signal Transductionmentioning

confidence: 99%

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Taste and pheromone perception in the fruit fly Drosophila melanogaster

Ebbs

Amrein

2007

Pflugers Arch - Eur J Physiol

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Taste is an essential sense for detection of nutrient-rich food and avoidance of toxic substances. The Drosophila melanogaster gustatory system provides an excellent model to study taste perception and taste-elicited behaviors. "The fly" is unique in the animal kingdom with regard to available experimental tools, which include a wide repertoire of molecular-genetic analyses (i.e., efficient production of transgenics and gene knockouts), elegant behavioral assays, and the possibility to conduct electrophysiological investigations. In addition, fruit flies, like humans, recognize sugars as a food source, but avoid bitter tasting substances that are often toxic to insects and mammals alike. This paper will present recent research progress in the field of taste and contact pheromone perception in the fruit fly. First, we shall describe the anatomical properties of the Drosophila gustatory system and survey the family of taste receptors to provide an appropriate background. We shall then review taste and pheromone perception mainly from a molecular genetic perspective that includes behavioral, electrophysiological and imaging analyses of wild type flies and flies with genetically manipulated taste cells. Finally, we shall provide an outlook of taste research in this elegant model system for the next few years.Keywords Drosophila . Gustatory receptor neurons . GTP-binding protein-coupled receptors Like most animals, Drosophila monitor their chemical world with two distinct senses: the olfactory system, which is used for the detection of volatile chemicals, and the gustatory (taste) system, which enables the fly to detect soluble compounds. The olfactory sensory system (or the fly nose) is comprised of two pairwise head appendages, the third segments of the antennae, and the maxillary palps (Fig. 1). These appendages are covered with hundreds of sensory hairs, each of which contains two to four olfactory sensory neurons (OSNs) [1]. In contrast, the gustatory system is widely distributed over the animal's body. The main taste organ, the proboscis or labial palps (i.e., the fly tongue), is located on the distal end of the labellum (also a head appendage), but flies, like many other insects, have taste sensilla on legs and wings and, in females, on the genitalia [1,2].The roles of the olfactory and taste systems are clearly separated with regard to the physical state of chemicals they detect (volatile vs solubilized). However, the two systems often cooperate to fulfill specific functions in related processes and behaviors, the most obvious of them being the location and identification of food. For example, chemical cues such as the specific odor of a flower and the sugar compounds present in its nectar are by nature associated with one another. Thus, the odor cue provides a primary sensory input for an insect such as a honeybee to locate a food source (nectar), whose particular chemical composition is subsequently verified by the taste system. Similarly, the typical odor of yeast, which produces high amounts of t...

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Section: Signal Transductionmentioning

confidence: 99%

“…A member of the mammalian Gα subfamily, Gs, stimulates adenylyl cyclase, thus elevating cAMP concentrations [78,79]. This cAMP signal transduction pathway has been shown to be involved in sugar perception [84][85][86].…”

Section: Signal Transductionmentioning

confidence: 99%

Taste and pheromone perception in the fruit fly Drosophila melanogaster

Ebbs

Amrein

2007

Pflugers Arch - Eur J Physiol

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“…Amphetamine, an indirect dopaminergic agonist, decreases PPI via dopamine D2 receptors (Ralph-Williams et al, 2002) that inhibit AC activity (Neves et al, 2002). Conversely, haloperidol, a typical antipsychotic that blocks D2 receptors (cf., Miyamoto et al, 2005) and increases cAMP signaling in forebrain structures (Berndt and Schwabe, 1973;Kaneko et al, 1992;Kaplan et al, 1999;Dwivedi et al, 2002; but see Kebabian et al, 1972;Carenzi et al, 1975), increases PPI (Ouagazzal et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, there appears to be a relationship between cAMP and PPI levels. Further, decreased levels of cAMP could result from either a hypoglutamatergic state (via reduced calcium/calmodulin stimulation of AC; Chetkovich and Sweatt, 1993) or a hyperdopaminergic state (via D2, 3, 4 receptor-mediated inhibition of AC; Neves et al, 2002), both of which are commonly hypothesized to contribute to endophenotypes of schizophrenia, such as PPI deficits (Sawa and Snyder, 2002). Interestingly, decreased cAMP levels have been observed in the cortex and striatum of patients with Tourette's syndrome (Singer et al, 1990) and reduced production of cAMP has been noted in platelets of patients with schizophrenia (Kaiya, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…Gas couples several neurotransmitter receptors, including the dopamine D1/ D5 receptors, to AC (Neves et al, 2002). Acutely, Gas stimulates AC resulting in increased levels of cAMP ( Figure 1a; Neves et al, 2002); however, compensatory degradation of cAMP by phosphodiesterases (PDEs) counteracts chronic Gas signaling in select cell types (Figure 1a; eg Lania et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Constitutive Activation of Gαs within Forebrain Neurons Causes Deficits in Sensorimotor Gating Because of PKA-Dependent Decreases in cAMP

Kelly

Isiegas

Cheung

et al. 2006

Neuropsychopharmacol

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Sensorimotor gating, the ability to automatically filter sensory information, is deficient in a number of psychiatric disorders, yet little is known of the biochemical mechanisms underlying this critical neural process. Previously, we reported that mice expressing a constitutively active isoform of the G-protein subunit Gas (Gas*) within forebrain neurons exhibit decreased gating, as measured by prepulse inhibition of acoustic startle (PPI). Here, to elucidate the biochemistry regulating sensorimotor gating and to identify novel therapeutic targets, we test the hypothesis that Gas* causes PPI deficits via brain region-specific changes in cyclic AMP (cAMP) signaling. As predicted from its ability to stimulate adenylyl cyclase, we find here that Gas* increases cAMP levels in the striatum. Suprisingly, however, Gas* mice exhibit reduced cAMP levels in the cortex and hippocampus because of increased cAMP phosphodiesterase (cPDE) activity. It is this decrease in cAMP that appears to mediate the effect of Gas* on PPI because Rp-cAMPS decreases PPI in C57BL/ 6J mice. Furthermore, the antipsychotic haloperidol increases both PPI and cAMP levels specifically in Gas* mice and the cPDE inhibitor rolipram also rescues PPI deficits of Gas* mice. Finally, to block potentially the pathway that leads to cPDE upregulation in Gas* mice, we coexpressed the R(AB) transgene (a dominant-negative regulatory subunit of protein kinase A (PKA)), which fully rescues the reductions in PPI and cAMP caused by Gas*. We conclude that expression of Gas* within forebrain neurons causes PPI deficits because of a PKAdependent decrease in cAMP and suggest that cAMP PDE inhibitors may exhibit antipsychotic-like therapeutic effects.

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Functional networks in mammalian cells

Xiong

Iyengar

2005

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

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The basic functional unit of multicellular organism is the cell. Cells are complex systems that perform many required fundamental functions such as environmental adaptation, energy utilization, proliferation, and differentiation in a regulated manner. Even cell death is often a controlled process. Cellular functions involve numerous components participating in a variety of processes. A critical aspect for normal cell functionality is the rigorous control of all cellular processes that may take place at different cellular locations at different rates and at different times. Such regulation is achieved by a central intracellular signaling network that receives and processes signals from both extracellular and intracellular sources. The processed signals are then used to regulate the different cellular machines such that they can function co‐operatively to evoke complex physiological responses. In order to achieve reliable functionality, the cell has developed multiple redundant systems that can regulate the cellular machines. Additionally, the systems are arranged in a modular fashion such that disturbances do not substantially propagate between modules. This architecture leads to a complex system where both robustness and fragility are dynamically balanced.

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G Protein Pathways

Cited by 1,120 publications

References 18 publications

Taste and pheromone perception in the fruit fly Drosophila melanogaster

Taste and pheromone perception in the fruit fly Drosophila melanogaster

Constitutive Activation of Gαs within Forebrain Neurons Causes Deficits in Sensorimotor Gating Because of PKA-Dependent Decreases in cAMP

Functional networks in mammalian cells

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