Opsin 3–G<sub>αs</sub> Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2

Wu, Amy D.; Dan, William; Zhang, Yi; Vemaraju, Shruti; Upton, Brian A.; Lang, Richard A.; Buhr, Ethan D.; Berkowitz, Dan E.; Gallos, George; Emala, Charles W.; Yim, Peter D.

doi:10.1165/rcmb.2020-0392oc

Cited by 15 publications

(13 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In smooth muscle, G i α signaling counteracts the G s α pathway and contributes to calcium sensitization ( Croxton et al, 1998 ; Billington and Penn, 2003 ). In contrast, smooth muscle OPN3 has been associated with G s α by coimmunoprecipitation and proximity ligation assay results in previous studies conducted in human myometrium and airway ( Yim et al, 2020 ; Wu et al, 2021 ). OPN3’s G protein specificity appears to vary not only between species, but also between tissue/cell types.…”

Section: Discussionmentioning

confidence: 62%

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

et al. 2021

Self Cite

View full text Add to dashboard Cite

Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon. Precontracted murine colon segments demonstrated blue light (BL) -mediated relaxation ex vivo. This photorelaxation was wavelength specific and was increased with the administration of the chromophore 9-cis retinal and a G protein receptor kinase 2 (GRK2) inhibitor. Light-mediated relaxation of the colon was not inhibited by L-NAME or tetrodotoxin (TTX). Furthermore, BL exposure in the presence of 9-cis retinal decreased the frequency of colonic migrating motor complexes (CMMC) in spontaneously contracting mouse colons ex vivo. These results demonstrate for the first time a receptor-mediated photorelaxation of colonic smooth muscle and implicate opsins as possible new targets in the treatment of spasmodic gastrointestinal dysmotility.

show abstract

Section: Discussionmentioning

confidence: 62%

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In vivo light exposure of mice revealed that white light increases brown fat energy expenditure supporting a thermogenic role for OPN3. Mechanistically, OPN3 may activate brown adipocytes through Gαs and the PKA pathway, which has been reported in airway smooth muscle cells [20]. Furthermore, in the absence of the Opn3 gene, the mitochondria in BAT present with disorganized organellar cristae indicating OPN3 has a key role in mitochondrial organization and/or maintenance [17].…”

Section: Opsinmentioning

confidence: 79%

Metabolic responses of light and taste receptors – unexpected actions of GPCRs in adipocytes

Ekechukwu

Christian

2021

Rev Endocr Metab Disord

View full text Add to dashboard Cite

The G-protein-coupled receptor (GPCR) superfamily includes sensory receptors that can detect and respond to taste and light. Recent investigations have identified key metabolic roles for such receptors in tissues considered ‘non-sensory’ such as adipose tissue. The major functions of white and brown adipose tissues include energy storage/release and thermogenesis, respectively. These processes are tightly controlled by GPCR pathways that serve to maintain energy homeostasis. Opsins 3 and 4 are GPCRs activated by blue light and in adipocytes control lipolysis as well as affect brown adipocyte activity. Furthermore, Opsin 3 signals to regulate the conversion of white to thermogenic beige/BRITE (Brown-in-white) adipocytes. Taste receptors that respond to fatty acids, sweet and bitter are expressed in adipocytes as well as in taste buds. Ffar2 and the long chain fatty acid receptor GPR120 are highly expressed in white adipocytes and the human tongue. In adipose tissue Ffar2 mediates the metabolic effects of butyrate and propionate produced by the gut microbiome. GPR120 is highly expressed in brown adipose tissue and regulates fatty acid oxidation and mitochondrial function. The type I taste receptor Tas1r3 senses sweet and umami, is expressed in adipocytes and on obesogenic diets Tas1r3 global gene knockout protects from metabolic dysfunction. Type II taste receptors that sense bitter are expressed by adipocytes and bitter agonists have been found to modulate adipocyte differentiation and lipid storage levels. This review explores recent unexpected findings of light and taste receptors in adipocytes and examines effects of their signaling in the control of adipose tissue biology.

show abstract

“…However, OPN3 and light were also demonstrated to interdependently modulate adaptive thermogenesis and glucose uptake in adipocytes, suggesting that OPN3 also functions in the photoreceptive pathway. Additional photoreceptive functions suggested for OPN3 include photorelaxation of smooth muscle within the uterus and airway ( Barreto Ortiz et al, 2018 ; Wu et al, 2020 ; Yim et al, 2019 , 2020 ). A non-light-dependent role for OPN3 has also been proposed in epidermal melanocytes, where it heterodimerizes with melanocortin 1 receptor to regulate pigmentation ( Ozdeslik et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Current data on OPN5 suggest that it functions only via light-mediated stimulation in the retina, skin, and hypothalamus ( Buhr et al, 2015 , 2019 ; Nguyen et al, 2019 ). Recent studies in smooth muscle and adipocytes demonstrate that OPN3 may also function in a light-dependent manner ( Nayak et al, 2020 ; Sato et al, 2020 ; Wu et al, 2020 ; Yim et al, 2019 , 2020 ); however, it has also been proposed that OPN3 has light-independent functions in skin, mediated via conjugation to other GPCRs such as the melanocortin 1 receptor ( Ozdeslik et al, 2019 ). Unlike RHO ( Jastrzebska et al, 2015 ; Ploier et al, 2016 ; Zhang et al, 2016 ), OPN3 does not appear to homodimerize ( Felce et al, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

et al. 2021

Self Cite

View full text Add to dashboard Cite

Animals have evolved light-sensitive G protein–coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express them. While many unique patterns of evolution have been identified in mammals for rod and cone opsins, far less is known about the atypical mammalian opsins. Using genomic data from over 400 mammalian species from 22 orders, unique patterns of evolution for each mammalian opsins were identified, including photoisomerases, RGR-opsin (RGR) and peropsin (RRH), as well as atypical opsins, encephalopsin (OPN3), melanopsin (OPN4), and neuropsin (OPN5). The results demonstrate that OPN5 and rhodopsin show extreme conservation across all mammalian lineages. The cone opsins, SWS1 and LWS, and the nonvisual opsins, OPN3 and RRH, demonstrate a moderate degree of sequence conservation relative to other opsins, with some instances of lineage-specific gene loss. Finally, the photoisomerase, RGR, and the best-studied atypical opsin, OPN4, have high sequence diversity within mammals. These conservation patterns are maintained in human populations. Importantly, all mammalian opsins retain key amino acid residues important for conjugation to retinal-based chromophores, permitting light sensitivity. These patterns of evolution are discussed along with known functions of each atypical opsin, such as in circadian or metabolic physiology, to provide insight into the observed patterns of evolutionary constraint.

show abstract

Opsin 3–G_αs Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2

Cited by 15 publications

References 31 publications

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Metabolic responses of light and taste receptors – unexpected actions of GPCRs in adipocytes

Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

Contact Info

Product

Resources

About

Opsin 3–Gαs Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2

Cited by 15 publications

References 31 publications

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Metabolic responses of light and taste receptors – unexpected actions of GPCRs in adipocytes

Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

Contact Info

Product

Resources

About

Opsin 3–G_αs Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2