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Intensiometric biosensors visualize the activity of multiple small GTPases in vivo

Ras and Rho small GTPases are critical for numerous cellular processes including cell division, migration, and intercellular communication. Despite extensive efforts to visualize the spatiotemporal activity of these proteins, achieving the sensitivity and dynamic range necessary for in vivo applicat...

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Autores principales: Kim, Jihoon, Lee, Sangkyu, Jung, Kanghoon, Oh, Won Chan, Kim, Nury, Son, Seungkyu, Jo, YoungJu, Kwon, Hyung-Bae, Heo, Won Do
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331645/
https://www.ncbi.nlm.nih.gov/pubmed/30643148
http://dx.doi.org/10.1038/s41467-018-08217-3
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author Kim, Jihoon
Lee, Sangkyu
Jung, Kanghoon
Oh, Won Chan
Kim, Nury
Son, Seungkyu
Jo, YoungJu
Kwon, Hyung-Bae
Heo, Won Do
author_facet Kim, Jihoon
Lee, Sangkyu
Jung, Kanghoon
Oh, Won Chan
Kim, Nury
Son, Seungkyu
Jo, YoungJu
Kwon, Hyung-Bae
Heo, Won Do
author_sort Kim, Jihoon
collection PubMed
description Ras and Rho small GTPases are critical for numerous cellular processes including cell division, migration, and intercellular communication. Despite extensive efforts to visualize the spatiotemporal activity of these proteins, achieving the sensitivity and dynamic range necessary for in vivo application has been challenging. Here, we present highly sensitive intensiometric small GTPase biosensors visualizing the activity of multiple small GTPases in single cells in vivo. Red-shifted sensors combined with blue light-controllable optogenetic modules achieved simultaneous monitoring and manipulation of protein activities in a highly spatiotemporal manner. Our biosensors revealed spatial dynamics of Cdc42 and Ras activities upon structural plasticity of single dendritic spines, as well as a broad range of subcellular Ras activities in the brains of freely behaving mice. Thus, these intensiometric small GTPase sensors enable the spatiotemporal dissection of complex protein signaling networks in live animals.
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spelling pubmed-63316452019-01-16 Intensiometric biosensors visualize the activity of multiple small GTPases in vivo Kim, Jihoon Lee, Sangkyu Jung, Kanghoon Oh, Won Chan Kim, Nury Son, Seungkyu Jo, YoungJu Kwon, Hyung-Bae Heo, Won Do Nat Commun Article Ras and Rho small GTPases are critical for numerous cellular processes including cell division, migration, and intercellular communication. Despite extensive efforts to visualize the spatiotemporal activity of these proteins, achieving the sensitivity and dynamic range necessary for in vivo application has been challenging. Here, we present highly sensitive intensiometric small GTPase biosensors visualizing the activity of multiple small GTPases in single cells in vivo. Red-shifted sensors combined with blue light-controllable optogenetic modules achieved simultaneous monitoring and manipulation of protein activities in a highly spatiotemporal manner. Our biosensors revealed spatial dynamics of Cdc42 and Ras activities upon structural plasticity of single dendritic spines, as well as a broad range of subcellular Ras activities in the brains of freely behaving mice. Thus, these intensiometric small GTPase sensors enable the spatiotemporal dissection of complex protein signaling networks in live animals. Nature Publishing Group UK 2019-01-14 /pmc/articles/PMC6331645/ /pubmed/30643148 http://dx.doi.org/10.1038/s41467-018-08217-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Jihoon
Lee, Sangkyu
Jung, Kanghoon
Oh, Won Chan
Kim, Nury
Son, Seungkyu
Jo, YoungJu
Kwon, Hyung-Bae
Heo, Won Do
Intensiometric biosensors visualize the activity of multiple small GTPases in vivo
title Intensiometric biosensors visualize the activity of multiple small GTPases in vivo
title_full Intensiometric biosensors visualize the activity of multiple small GTPases in vivo
title_fullStr Intensiometric biosensors visualize the activity of multiple small GTPases in vivo
title_full_unstemmed Intensiometric biosensors visualize the activity of multiple small GTPases in vivo
title_short Intensiometric biosensors visualize the activity of multiple small GTPases in vivo
title_sort intensiometric biosensors visualize the activity of multiple small gtpases in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331645/
https://www.ncbi.nlm.nih.gov/pubmed/30643148
http://dx.doi.org/10.1038/s41467-018-08217-3
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