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Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein
Heterotrimeric G-proteins are signal transducers involved in mediating the action of many natural extracellular stimuli and many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515630/ https://www.ncbi.nlm.nih.gov/pubmed/32936073 http://dx.doi.org/10.7554/eLife.60155 |
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author | Garcia-Marcos, Mikel Parag-Sharma, Kshitij Marivin, Arthur Maziarz, Marcin Luebbers, Alex Nguyen, Lien T |
author_facet | Garcia-Marcos, Mikel Parag-Sharma, Kshitij Marivin, Arthur Maziarz, Marcin Luebbers, Alex Nguyen, Lien T |
author_sort | Garcia-Marcos, Mikel |
collection | PubMed |
description | Heterotrimeric G-proteins are signal transducers involved in mediating the action of many natural extracellular stimuli and many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here, we developed LOV2GIVe, an engineered modular protein that allows the activation of heterotrimeric G-proteins with blue light. This optogenetic construct relies on a versatile design that differs from tools previously developed for similar purposes, that is metazoan opsins, which are light-activated G-protein-coupled receptors (GPCRs). Instead, LOV2GIVe consists of the fusion of a G-protein activating peptide derived from a non-GPCR regulator of G-proteins to a small plant protein domain, such that light uncages the G-protein activating module. Targeting LOV2GIVe to cell membranes allowed for light-dependent activation of Gi proteins in different experimental systems. In summary, LOV2GIVe expands the armamentarium and versatility of tools available to manipulate heterotrimeric G-protein activity. |
format | Online Article Text |
id | pubmed-7515630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-75156302020-09-25 Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein Garcia-Marcos, Mikel Parag-Sharma, Kshitij Marivin, Arthur Maziarz, Marcin Luebbers, Alex Nguyen, Lien T eLife Biochemistry and Chemical Biology Heterotrimeric G-proteins are signal transducers involved in mediating the action of many natural extracellular stimuli and many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here, we developed LOV2GIVe, an engineered modular protein that allows the activation of heterotrimeric G-proteins with blue light. This optogenetic construct relies on a versatile design that differs from tools previously developed for similar purposes, that is metazoan opsins, which are light-activated G-protein-coupled receptors (GPCRs). Instead, LOV2GIVe consists of the fusion of a G-protein activating peptide derived from a non-GPCR regulator of G-proteins to a small plant protein domain, such that light uncages the G-protein activating module. Targeting LOV2GIVe to cell membranes allowed for light-dependent activation of Gi proteins in different experimental systems. In summary, LOV2GIVe expands the armamentarium and versatility of tools available to manipulate heterotrimeric G-protein activity. eLife Sciences Publications, Ltd 2020-09-16 /pmc/articles/PMC7515630/ /pubmed/32936073 http://dx.doi.org/10.7554/eLife.60155 Text en © 2020, Garcia-Marcos et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Garcia-Marcos, Mikel Parag-Sharma, Kshitij Marivin, Arthur Maziarz, Marcin Luebbers, Alex Nguyen, Lien T Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein |
title | Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein |
title_full | Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein |
title_fullStr | Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein |
title_full_unstemmed | Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein |
title_short | Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein |
title_sort | optogenetic activation of heterotrimeric g-proteins by lov2give, a rationally engineered modular protein |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515630/ https://www.ncbi.nlm.nih.gov/pubmed/32936073 http://dx.doi.org/10.7554/eLife.60155 |
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