Evidence map›Paper›PMID 30610117›Full record

ArticleThe Journal of biological chemistry2019

Multidimensional screening yields channelrhodopsin variants having improved photocurrent and order-of-magnitude reductions in calcium and proton currents.

Yong Ku Cho, Demian Park, Aimei Yang, Fei Chen, Amy S Chuong, Nathan C Klapoetke, Edward S Boyden

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Structure-Function Relationship of Channelrhodopsins.Advances in experimental medicine and biology · 2021
    Review
  10. Optogenetic Modulation of Ion Channels by Photoreceptive Proteins.Advances in experimental medicine and biology · 2021
    Review
  11. Toward Multiplexed Optogenetic Circuits.Frontiers in bioengineering and biotechnology · 2021
    Review
  12. Action potentials in Xenopus oocytes triggered by blue light.The Journal of general physiology · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Making light work of fine-tuning channelrhodopsins.The Journal of biological chemistry · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Yong Ku ChoFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139.ORCID 0000-0001-5621-521X
Demian ParkFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139.
Aimei YangFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139.
Fei ChenFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139.
Amy S ChuongFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139.
Nathan C KlapoetkeFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139.
Edward S BoydenFrom the MIT Media Lab, McGovern Institute, and Koch Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139 esb@media.mit.edu.
McGovern Institute for Brain Research · US

Funding

Novel Platforms for Systematic Optical Control of Complex Neural Circuits In VivoR01DA029639 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2010 to 2023
$6.7M
Novel Tools and Principles for Precisely Controlling Brain ActivityDP2OD002002 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2007 to 2007
$2.5M
Genetically-Encoded Tools for Manipulation of Ion Channel and Receptor FunctionsR01NS075421 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2011 to 2014
$1.3M
NIDA NIH HHS R01 DA029639NIH HHS DP2 OD002002NINDS NIH HHS R01 NS075421
6 · The paper itself

Abstract

Channelrhodopsins (ChRs) are light-gated ion channels in widespread use in neuroscience for mediating the genetically targetable optical control of neurons (optogenetics). ChRs pass multiple kinds of ions, and although nonspecific ChR-mediated conductance is not an issue in many neuroscience studies, conductance of calcium and protons, which can mediate diverse cellular signals, may be undesirable in some instances. Here, we turned our attention to the creation of ChRs that have high cation photocurrent but pass fewer calcium ions and protons. We developed an automated, time-resolved screening method capable of rapidly phenotyping channelrhodopsin-2 (ChR2) variants. We found substitution mutations throughout ChR2 that could boost current while altering ion selectivity and observed that the mutations that reduced calcium or proton conductance have additive effects. By combining four mutations, we obtained a ChR, ChromeQ, with improved photocurrent that possesses order-of-magnitude reductions in calcium and proton conductance and high fidelity in driving repetitive action potentials in neurons. The approach presented here offers a viable pathway toward customization of complex physiological properties of optogenetic tools. We propose that our screening method not only enables elucidation of new ChR variants that affect microbial opsin performance but may also reveal new principles of optogenetic protein engineering.

Indexed as

Electric ConductivityGenetic VariationProtonsAnimalsCalciumChannelrhodopsinsCloning, MolecularFluorescenceHEK293 CellsHumansOxidation-ReductionPhenotypePhotochemical ProcessesCalciumChannelrhodopsinsProtonscalciumchannelrhodopsinneurobiologyoptogeneticsphysiologyprotein engineeringprotonscreening

Identifiers

PMID30610117
PMCPMC6422097
OpenAlexW2908102740

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.