G Protein Selectivity Is Regulated by Multiple Intracellular Regions of GPCRs

Wong, Sharon

doi:10.1159/000068914

Cited by 124 publications

(103 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%

“…Other long chain hydrocarbons are thought to be detected by other members of the GR68a family, which include GR32a and GR39a.a-a.d dissociates from the βγ complex, enabling both the α and βγ subunits to activate downstream signaling molecules. Despite expressing thousands of GPCRs, mammals have only four subfamilies of α subunits that are grouped according to the signaling pathway an α subunit activates [78].…”

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%

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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%

Section: Signal Transductionmentioning

confidence: 99%

See 1 more Smart Citation

Taste and pheromone perception in the fruit fly Drosophila melanogaster

Ebbs

Amrein

2007

Pflugers Arch - Eur J Physiol

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“…We next used a microscale thermophoresis technique (35) to investigate the ability of the TSHR ICD mimetics to bind recombinant purified Ga subunits. TSHR is remarkable in its ability to activate all known G protein isoforms (21)(22)(23). Fluorescently labeled Ga subunits (Ga-(s), Ga-(i2), and Ga-(q)) were titrated with increasing concentrations (0.1-100 mM) of unlabeled mimetic proteins.…”

Section: Construction Of Tshr Icd Mimeticsmentioning

confidence: 99%

“…As a model GPCR, we used thyroid-stimulating hormone receptor (TSHR), a GPCR that has well-documented promiscuous G protein-coupling behavior and is able to activate all known G protein isoforms (21)(22)(23). The respective physiological/pathological consequences of the activation of individual isoforms of G proteins by TSHR, however, remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Construction of Structural Mimetics of the Thyrotropin Receptor Intracellular Domain

Press

Zvagelsky

Vyazmensky

et al. 2016

Biophysical Journal

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The signaling of a G protein-coupled receptor (GPCR) is dictated by the complementary responsiveness of interacting intracellular effectors such as G proteins. Many GPCRs are known to couple to more than one G protein subtype and induce a multitude of signaling pathways, although the in vivo relevance of particular pathways is mostly unrecognized. Dissecting GPCR signaling in terms of the pathways that are activated will boost our understanding of the molecular fundamentals of hormone action. The structural determinants governing the selectivity of GPCR/G protein coupling, however, remain obscure. Here, we describe the design of soluble GPCR mimetics to study the details of the interplay between G-proteins and activators. We constructed functional mimetics of the intracellular domain of a model GPCR, the thyrotropin receptor. We based the construction on a unique scaffold, 6-Helix, an artificial protein that was derived from the elements of the trimer-of-hairpins structure of HIV gp41 and represents a bundle of six a-helices. The 6-Helix scaffold, which endowed the substituted thyrotropin receptor intracellular domain elements with spatial constraints analogous to those found in native receptors, enabled the reconstitution of a microdomain that consists of intracellular loops 2 and 3, and is capable of binding and activating Ga-(s). The 6-Helix-based mimetics could be used as a platform to study the molecular basis of GPCR/G protein recognition. Such knowledge could help investigators develop novel therapeutic strategies for GPCR-related disorders by targeting the GPCR/G protein interfaces and counteracting cellular dysfunctions via focused tuning of GPCR signaling.

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Odour perception: A review of an intricate signalling pathway

Tromelin

2015

Flavour & Fragrance J

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The perception of odours is the result of the complex processing of a signal, which initiates at peripheral receptors and ends in the brain. Along this pathway, olfactory signal processing proceeds through several steps; each step possesses its own complexity, and all steps are also intricately connected. This review aims to describe the main intricate steps of olfactory processing in mammals, some of which remain unclear, and the close associations and overlapping nature of these steps. The causes of both the complexity and the variability of olfactory signals are examined: the nature of olfactory receptors, involving the diversity of the genome; the spatial organization of the olfactory epithelium (OE) and the olfactory bulb (OB); connections in the OB and from the OB to the brain; integration and processing in the brain, which leads to the final perception of odours; and odour recognition and odour identification, which is associated with the difficulty to verbalize a reliable description of the perception in humans. Finally, the last part of this review encompasses recent progress made to decipher and understand olfactory coding and focuses on computational approaches

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G Protein Selectivity Is Regulated by Multiple Intracellular Regions of GPCRs

Cited by 124 publications

References 50 publications

Taste and pheromone perception in the fruit fly Drosophila melanogaster

Taste and pheromone perception in the fruit fly Drosophila melanogaster

Construction of Structural Mimetics of the Thyrotropin Receptor Intracellular Domain

Odour perception: A review of an intricate signalling pathway

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