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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...

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Autores principales: Garcia-Marcos, Mikel, Parag-Sharma, Kshitij, Marivin, Arthur, Maziarz, Marcin, Luebbers, Alex, Nguyen, Lien T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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