2019
DOI: 10.1016/j.cell.2019.02.023
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Engineering a Model Cell for Rational Tuning of GPCR Signaling

Abstract: Summary G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We de… Show more

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Cited by 172 publications
(251 citation statements)
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References 117 publications
(176 reference statements)
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“…Thus, by using a reporter gene at the end of the pheromone response pathway, a heterologous yeast strain was obtained that acted as a melatonin sensor. By employing the green fluorescent protein as a reporter, the authors detected melatonin production by yeasts using a microplate reader without having to process the sample, but directly from the supernatant (40). The second method was set up to detect melatonin in fermented beverages, and it involved mammalian melatonin receptor MTNR1B and cell lines as a sensor.…”
Section: Development and Optimization Of Analytical Techniques To Detmentioning
confidence: 99%
“…Thus, by using a reporter gene at the end of the pheromone response pathway, a heterologous yeast strain was obtained that acted as a melatonin sensor. By employing the green fluorescent protein as a reporter, the authors detected melatonin production by yeasts using a microplate reader without having to process the sample, but directly from the supernatant (40). The second method was set up to detect melatonin in fermented beverages, and it involved mammalian melatonin receptor MTNR1B and cell lines as a sensor.…”
Section: Development and Optimization Of Analytical Techniques To Detmentioning
confidence: 99%
“…way components(Ostrov et al, 2017;Shaw et al, 2019) may not function as well in strains with altered sterol content.Importantly, recent studies have utilised the yeast pheromone response to separate yeast growth from product generation. The delay of production until cells have grown to a particular cell density (reviewed inVenayak, Anesiadis, Cluett, & Mahadevan, 2015) is advantageous if transgene expression and/or the heterologous product is toxic or if production severely starves the cells of metabolites required for growth Yu et al (2017).…”
mentioning
confidence: 99%
“…The approach of Ostrov and colleagues using GPCRs is equally versatile and can be adapted to detect target molecules that we have not yet thought of [33]. Similarly, Shaw and colleagues engineered a modified S. cerevisiae cell as a platform for biosensors construction by rational tuning of GPCR signaling [92,93].…”
Section: Technological Developmentsmentioning
confidence: 99%