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A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling

Overview of attention for article published in BMC Biology, January 2018
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  • Good Attention Score compared to outputs of the same age (69th percentile)

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3 tweeters
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1 patent

Citations

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14 Dimensions

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60 Mendeley
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Title
A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling
Published in
BMC Biology, January 2018
DOI 10.1186/s12915-017-0475-2
Pubmed ID
Authors

Edward R. Ballister, Jessica Rodgers, Franck Martial, Robert J. Lucas

Abstract

Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs) that enable optogenetic control over the major heterotrimeric G-protein signaling pathways in animal cells. As such, opsins have potential applications in both biomedical research and therapy. Selecting the opsin with the best balance of activity and selectivity for a given application requires knowing their ability to couple to a full range of relevant Gα subunits. We present the GsX assay, a set of tools based on chimeric Gs subunits that transduce coupling of opsins to diverse G proteins into increases in cAMP levels,  measured with a real-time reporter in living cells. We use this assay to compare coupling to Gi/o/t across a panel of natural and chimeric opsins selected for potential application in gene therapy for retinal degeneration. Of the opsins tested, wild-type human rod opsin had the highest activity for chimeric Gs proxies for Gi and Gt (Gsi and Gst) and was matched in Go proxy (Gso) activity only by a human rod opsin/scallop opsin chimera. Rod opsin drove roughly equivalent responses via Gsi, Gso, and Gst, while cone opsins showed much lower activities with Gso than Gsi or Gst, and a human rod opsin/amphioxus opsin chimera demonstrated higher activity with Gso than with Gsi or Gst. We failed to detect activity for opsin chimeras bearing three intracellular fragments of mGluR6, and observed unexpectedly complex response profiles for scallop and amphioxus opsins thought to be specialized for Go. These results identify rod opsin as the most potent non-selective Gi/o/t-coupled opsin, long-wave sensitive cone opsin as the best for selectively activating Gi/t over Go, and a rod opsin/amphioxus opsin chimera as the best choice for selectively activating Go over Gi/t.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 60 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 28%
Researcher 9 15%
Student > Bachelor 8 13%
Student > Master 6 10%
Other 4 7%
Other 5 8%
Unknown 11 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 28%
Neuroscience 11 18%
Agricultural and Biological Sciences 10 17%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Medicine and Dentistry 3 5%
Other 3 5%
Unknown 13 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2020.
All research outputs
#4,767,291
of 17,366,233 outputs
Outputs from BMC Biology
#943
of 1,499 outputs
Outputs of similar age
#114,435
of 375,057 outputs
Outputs of similar age from BMC Biology
#1
of 1 outputs
Altmetric has tracked 17,366,233 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,499 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 19.7. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 375,057 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them