Ontogeny of GTP-binding proteins, Gi and G0, in rat retina

Oguni, Masami; Shinohara, Haruo; Asano, Taku; Kato, Kanefusa; Setogawa, Tomoichi

doi:10.1007/bf02484406

Cited by 10 publications

(3 citation statements)

References 24 publications

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“…It is known that rhodopsin activates G i and G o efficiently in vitro [53], [54]. Notably, G i2 is expressed in the photoreceptors [55]. Therefore, it may be a target for rhodopsin activation in vivo .…”

Section: Discussionmentioning

confidence: 99%

Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Concepcion

Chen

2010

PLoS ONE

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Q344ter is a naturally occurring rhodopsin mutation in humans that causes autosomal dominant retinal degeneration through mechanisms that are not fully understood, but are thought to involve an early termination that removed the trafficking signal, QVAPA, leading to its mislocalization in the rod photoreceptor cell. To better understand the disease mechanism(s), transgenic mice that express Q344ter were generated and crossed with rhodopsin knockout mice. Dark-reared Q344terrho+/− mice exhibited retinal degeneration, demonstrating that rhodopsin mislocalization caused photoreceptor cell death. This degeneration is exacerbated by light-exposure and is correlated with the activation of transducin as well as other G-protein signaling pathways. We observed numerous sub-micrometer sized vesicles in the inter-photoreceptor space of Q344terrho+/− and Q344terrho−/− retinas, similar to that seen in another rhodopsin mutant, P347S. Whereas light microscopy failed to reveal outer segment structures in Q344terrho−/− rods, shortened and disorganized rod outer segment structures were visible using electron microscopy. Thus, some Q344ter molecules trafficked to the outer segment and formed disc structures, albeit inefficiently, in the absence of full length wildtype rhodopsin. These findings helped to establish the in vivo role of the QVAPA domain as well as the pathways leading to Q344ter-induced retinal degeneration.

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Section: Discussionmentioning

confidence: 99%

Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Concepcion

Chen

2010

PLoS ONE

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“…G iα3 was not detected by immunoblotting or with subsequent immunohistochemical studies in the rabbit retina. A study by Oguni et al . (1996) examined the distribution and the levels of G i1/3α , G i2α , G i3α and G oα during development in the rat retina.…”

Section: Discussionmentioning

confidence: 99%

Somatostatin receptors (sst₂) are coupled to G_o and modulate GTPase activity in the rabbit retina

Vasilaki

Georgoussi

Thermos

2003

Journal of Neurochemistry

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The role of somatostatin and its mechanism of action in the retina remains an important target for investigation. Biochemical and pharmacological studies were engaged to characterize the somatostatin receptors in the rabbit retina, and their coupling to G-proteins. The ability of selective ligands to inhibit [ 125 I]Tyr11-somatostatin-14 binding to rabbit retinal membranes was examined. The sst 2 analogues SMS201-995, MK678, and BIM23014, displayed IC 50 values of 0.28 ± 0.12, 0.04 ± 0.01 and 1.57 ± 0.39 nM, respectively. The sst 1 analogue CH275 moderately displaced the [ 125 I]Tyr11-somatostatin-14 binding, while selective analogues for sst 3 , sst 4 and sst 5 had minimal effect. Immunoblotting and/or immunohistochemistry studies revealed the presence of the pertussis toxin sensitive G i1/2 , and G o proteins, as well as G s . Somatostatin-14 and MK678 stimulated GTPase activity in a concentration-dependent manner with EC 50 values of 42.8 ± 16.8 and 70.0 ± 16.5 nM, respectively, thus supporting the functional coupling between the receptor and the G-proteins. CH275 stimulated the GTPase activity moderately, in agreement with its binding profile. The antisera raised against G oa and G i1/2a inhibited the somatostatin-induced high-affinity GTPase activity, but only anti-G oa inhibited the MK678 stimulation of the enzyme. These results suggest that somatostatin mediates its actions in the rabbit retina by interacting mainly with sst 2 receptors that couple to G oa .

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“…The G αi proteins also locate to intracellular membranes including Golgi and endosomal membranes ( Gohla et al, 2007 ; Young et al, 2008 ) and were found to be associated with membrane trafficking and fusion events ( Young et al, 2008 ). In addition, G αi3 is expressed in fetal and adult human RPE cells and the inner neural retina ( Jiang et al, 1991 ; Oguni et al, 1996 ; Young et al, 2008 ). By studying the RPE density and morphology of melanosomes of G αi3 −/− and GP143 −/− knockout mice, the authors were able to observe the same phenotype in both mice genotypes ( Young et al, 2008 ).…”

Section: Gpr143 Functionmentioning

confidence: 99%

The Many Faces of G Protein-Coupled Receptor 143, an Atypical Intracellular Receptor

Bueschbell

Manga

Schiedel

2022

Front. Mol. Biosci.

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GPCRs transform extracellular stimuli into a physiological response by activating an intracellular signaling cascade initiated via binding to G proteins. Orphan G protein-coupled receptors (GPCRs) hold the potential to pave the way for development of new, innovative therapeutic strategies. In this review we will introduce G protein-coupled receptor 143 (GPR143), an enigmatic receptor in terms of classification within the GPCR superfamily and localization. GPR143 has not been assigned to any of the GPCR families due to the lack of common structural motifs. Hence we will describe the most important motifs of classes A and B and compare them to the protein sequence of GPR143. While a precise function for the receptor has yet to be determined, the protein is expressed abundantly in pigment producing cells. Many GPR143 mutations cause X-linked Ocular Albinism Type 1 (OA1, Nettleship-Falls OA), which results in hypopigmentation of the eyes and loss of visual acuity due to disrupted visual system development and function. In pigment cells of the skin, loss of functional GPR143 results in abnormally large melanosomes (organelles in which pigment is produced). Studies have shown that the receptor is localized internally, including at the melanosomal membrane, where it may function to regulate melanosome size and/or facilitate protein trafficking to the melanosome through the endolysosomal system. Numerous additional roles have been proposed for GPR143 in determining cancer predisposition, regulation of blood pressure, development of macular degeneration and signaling in the brain, which we will briefly describe as well as potential ligands that have been identified. Furthermore, GPR143 is a promiscuous receptor that has been shown to interact with multiple other melanosomal proteins and GPCRs, which strongly suggests that this orphan receptor is likely involved in many different physiological actions.

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Ontogeny of GTP-binding proteins, Gi and G0, in rat retina

Cited by 10 publications

References 24 publications

Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Somatostatin receptors (sst₂) are coupled to G_o and modulate GTPase activity in the rabbit retina

The Many Faces of G Protein-Coupled Receptor 143, an Atypical Intracellular Receptor

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Ontogeny of GTP-binding proteins, Gi and G0, in rat retina

Cited by 10 publications

References 24 publications

Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Somatostatin receptors (sst2) are coupled to Go and modulate GTPase activity in the rabbit retina

The Many Faces of G Protein-Coupled Receptor 143, an Atypical Intracellular Receptor

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Somatostatin receptors (sst₂) are coupled to G_o and modulate GTPase activity in the rabbit retina