The G Protein-Coupled Receptor Rhodopsin: A Historical Perspective

Hofmann, Lukas; Palczewski, Krzysztof

doi:10.1007/978-1-4939-2330-4_1

Cited by 18 publications

(13 citation statements)

References 95 publications

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“…Endogenous or exogenous bioactive ligands activate cell surface receptors and initiate a cascade that amplifies the first messenger action via signal transduction pathways (reviewed by Hofmann and Palczewski, 2015 ). First, the membrane signaling proteins are activated, and then they mediate subsequent reactions, following membrane receptor activation.…”

Section: Gintonin Has a Specific Signaling Pathway For Activation Of mentioning

confidence: 99%

Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions

et al. 2015

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Ginseng, the root of Panax ginseng, is used as a traditional medicine. Despite the long history of the use of ginseng, there is no specific scientific or clinical rationale for ginseng pharmacology besides its application as a general tonic. The ambiguous description of ginseng pharmacology might be due to the absence of a predominant active ingredient that represents ginseng pharmacology. Recent studies show that ginseng abundantly contains lysophosphatidic acids (LPAs), which are phospholipid-derived growth factor with diverse biological functions including those claimed to be exhibited by ginseng. LPAs in ginseng form a complex with ginseng proteins, which can bind and deliver LPA to its cognate receptors with a high affinity. As a first messenger, gintonin produces second messenger Ca2+ via G protein-coupled LPA receptors. Ca2+ is an intracellular mediator of gintonin and initiates a cascade of amplifications for further intercellular communications by activation of Ca2+-dependent kinases, receptors, gliotransmitter, and neurotransmitter release. Ginsenosides, which have been regarded as primary ingredients of ginseng, cannot elicit intracellular [Ca2+]i transients, since they lack specific cell surface receptor. However, ginsenosides exhibit non-specific ion channel and receptor regulations. This is the key characteristic that distinguishes gintonin from ginsenosides. Although the current discourse on ginseng pharmacology is focused on ginsenosides, gintonin can definitely provide a mode of action for ginseng pharmacology that ginsenosides cannot. This review article introduces a novel concept of ginseng ligand-LPA receptor interaction and proposes to establish a paradigm that shifts the focus from ginsenosides to gintonin as a major ingredient representing ginseng pharmacology.

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Section: Gintonin Has a Specific Signaling Pathway For Activation Of mentioning

confidence: 99%

Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions

et al. 2015

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“…Even with high resolution structures available, the mechanistic details which underlie the actual transduction of signal initiated by ligand binding remain elusive. While rhodopsin in the retina does not respond to a diffusible ligand (the rhodopsin activation cycle begins with photon absorption driven isomerization of covalently-bound 11- cis -retinal chromophore to all- trans ), it contains many of the conserved motifs important for GPCR activation and its relative ease of purification has served as a prototypical GPCR for understanding structure and function (Hofmann and Palczewski, 2015). …”

Section: Introductionmentioning

confidence: 99%

The High-Resolution Structure of Activated Opsin Reveals a Conserved Solvent Network in the Transmembrane Region Essential for Activation

2015

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Rhodopsin, a light-activated G protein coupled receptor (GPCR), has been the subject of numerous biochemical and structural investigations, serving as a model receptor for GPCRs and their activation. Herein we present the 2.3 Å resolution structure of native-source rhodopsin stabilized in a conformation competent for G protein binding. An extensive water-mediated hydrogen bond network linking the chromophore binding site to the site of G protein binding is observed, providing connections to conserved motifs essential for GPCR activation. Comparison of this extensive solvent mediated hydrogen-bonding network to the positions of ordered solvent in earlier crystallographic structures of rhodopsin photointermediates reveals both static structural and dynamic functional water-protein interactions present during the activation process. When taken with observations that solvent occupies similar positions in the structures of other GPCRs, these analyses strongly support an integral role for this dynamic ordered water network in both rhodopsin and GPCR activation.

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“…In physiological level, one major protein that uptakes the intracellular calcium ion is rhodopsin. Rhodopsin is a GPCR (G-protein coupled receptor) that converts light stimuli to the cGMP activation followed by the intracellular calcium uptake (29). In our immunoprecipitation analysis, rhodopsin interacted with Prom1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Membrane Protrusion Formation Mediated by Rho/ROCK Signalling and Modulation of Chloride Flux

Hori

Nishide²,

Yasukuni

et al. 2019

Preprint

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33Membrane protrusion is an important structural property associated with various cellular functions. The 34 pentaspan membrane protein Prominin-1 (Prom1/CD133) is known to be localised to the protrusions and 35 plays a pivotal role in migration and the determination of cellular morphology; however, the underlying 36 mechanisms have been elusive. Here, we demonstrate that Prom1 is sufficient to trigger membrane 37 protrusion formation. Overexpression of Prom1 in the RPE-1 cells triggers multiple long cholesterol-38 enriched protrusions, independently from actin and tubulin polymerisation. For this protrusion formation, 39 the five amino acid stretch located at the carboxyl cytosolic region is essential. Moreover, the small GTPase 40Rho and its effector kinase ROCK are essential for this protrusion formation, and the intersection point of 41 active Rho and Prom1 is where the protrusion formation initiates. Importantly, Prom1 causes the chloride42 ion efflux induced by calcium ion uptake, and protrusion formation is closely associated with the chloride 43 efflux activity. Altogether, this study has elucidated that Prom1 plays critical roles for the membrane 44 morphology and chloride ion flux.48 curvature and invagination. 49Cilia, cytonemes and microvilli are representative protrusions (1). Cilia contain microtubules and 50 act as antennae for physical stimuli or extracellular signal molecules. Cytonemes, which comprise actin, are 51 presumed to transport the signal molecules distant from the cell body. Microvilli, which are often formed at 52 the luminal membrane in the intestine, are also membrane protrusions rich in cholesterol (2), and are formed 53 to widen the cell surface and to efficiently incorporate extracellular materials into the body. In general, these 54 protrusions transduce essential information into the cells in order to decide the cell response to these stimuli. 55Therefore, the mechanisms for cell shape regulation is one of the central questions of cell biology. 56In the vertebrate retina, the photoreceptor cell has a long cell shape, and is divided into different 57 functional compartments. Among these compartments, the discs, which are responsible for initial light 58 perception, are continuously formed in the outer segment. Disc formation commences with the curvature of 59 the membrane at the adjacent region of the connecting cilium, which is then separated from the cell 60 membrane to form microvesicles in the photoreceptor cell (3). 61Prominin-1 (CD133, Prom1) encodes a pentaspan transmembrane glycoprotein, highly expressed 62 in the retina, kidney, and testis (4). Prom1 is localised at the connecting cilium and in the outer segment (5), 63 and is recognised as a crucial gene for the homeostasis of photoreceptor cells (5). The loss of Prom1 function 64 leads to photoreceptor degeneration (6-8). In pedigrees with mutations in the Prom1 gene, individuals 65 carrying the homologous mutation suffer from inherited macular dystrophies termed as Stargardt's disease 66 and retinitis pigmentosa (RP)...

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The G Protein-Coupled Receptor Rhodopsin: A Historical Perspective

Cited by 18 publications

References 95 publications

Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions

Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions

The High-Resolution Structure of Activated Opsin Reveals a Conserved Solvent Network in the Transmembrane Region Essential for Activation

Membrane Protrusion Formation Mediated by Rho/ROCK Signalling and Modulation of Chloride Flux

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