{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T21:54:12Z","timestamp":1785621252308,"version":"3.56.0"},"reference-count":101,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>G protein-coupled receptors (GPCRs) are crucial sensors of extracellular signals in eukaryotes, and direct measurement of GPCR-mediated signaling is useful for high-throughput mutational studies. However, this is particularly difficult for the light-activated GPCR rhodopsin...<\/jats:p><jats:p>G protein-coupled receptors (GPCRs) are crucial sensors of extracellular signals in eukaryotes, with multiple GPCR mutations linked to human diseases. With the growing number of sequenced human genomes, determining the pathogenicity of a mutation is challenging, but can be aided by a direct measurement of GPCR-mediated signaling. This is particularly difficult for the visual pigment rhodopsin\u2014a GPCR activated by light\u2014for which hundreds of mutations have been linked to inherited degenerative retinal diseases such as retinitis pigmentosa. In this study, we successfully engineered, for the first time, activation by human rhodopsin of the yeast mating pathway, resulting in signaling via a fluorescent reporter. We combine this novel assay for rhodopsin light-dependent activation with studies of subcellular localization, and the upregulation of the unfolded protein response in response to misfolded rhodopsin protein. We use these assays to characterize a panel of rhodopsin mutations with known molecular phenotypes, finding that rhodopsin maintains a similar molecular phenotype in yeast, with some interesting differences. Furthermore, we compare our assays in yeast with clinical phenotypes from patients with novel disease-linked mutations. We demonstrate that our engineered yeast strain can be useful in rhodopsin mutant classification, and in helping to determine the molecular mechanisms underlying their pathogenicity. This approach may also be applied to better understand the clinical relevance of other human GPCR mutations, furthering the use of yeast as a tool for investigating molecular mechanisms relevant to human disease.<\/jats:p>","DOI":"10.1534\/genetics.118.301733","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T03:45:14Z","timestamp":1543981514000},"page":"597-615","source":"Crossref","is-referenced-by-count":20,"title":["Coupling of Human Rhodopsin to a Yeast Signaling Pathway Enables Characterization of Mutations Associated with Retinal Disease"],"prefix":"10.1093","volume":"211","author":[{"given":"Benjamin M","family":"Scott","sequence":"first","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven K","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihar","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdiwahab Y","family":"Moalim","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey V","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Heon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology , Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio G","family":"Peisajovich","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda S W","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology , University of Toronto, Ontario M5S 3G5, Canada"},{"name":"Department of Ecology and Evolutionary Biology , University of Toronto, Ontario M5S 3G5, Canada"},{"name":"Centre for the Analysis of Genome Evolution and Function , University of Toronto, Ontario M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"2023031004553792500_","doi-asserted-by":"publisher","first-page":"25406","DOI":"10.1074\/jbc.271.41.25406","article-title":"Modulation of GDP release from transducin by the conserved Glu134-Arg135 sequence in rhodopsin.","volume":"271","author":"Acharya","year":"1996","journal-title":"J. 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