Intensiometric biosensors visualize the activity of multiple small GTPases in vivo

Jihoon Kim, Sangkyu Lee, Kanghoon Jung, Won Chan Oh, Nury Kim, Seungkyu Son, Young Ju Jo, Hyungbae Kwon, Won Do Heo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number211
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Fingerprint

Monomeric GTP-Binding Proteins
Biosensing Techniques
bioinstrumentation
Biosensors
proteins
Optogenetics
Dissection
rho GTP-Binding Proteins
Dendritic Spines
Proteins
Sensors
cell division
dissection
spine
Cell Division
Cell Movement
sensors
Plasticity
Brain
Animals

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kim, J., Lee, S., Jung, K., Oh, W. C., Kim, N., Son, S., ... Do Heo, W. (2019). Intensiometric biosensors visualize the activity of multiple small GTPases in vivo. Nature communications, 10(1), [211]. https://doi.org/10.1038/s41467-018-08217-3

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, Young Ju; Kwon, Hyungbae; Do Heo, Won.

In: Nature communications, Vol. 10, No. 1, 211, 01.12.2019.

Research output: Contribution to journalArticle

Kim, Jihoon ; Lee, Sangkyu ; Jung, Kanghoon ; Oh, Won Chan ; Kim, Nury ; Son, Seungkyu ; Jo, Young Ju ; Kwon, Hyungbae ; Do Heo, Won. / Intensiometric biosensors visualize the activity of multiple small GTPases in vivo. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{7f356eafc4f74d97a8a408f30997a941,
title = "Intensiometric biosensors visualize the activity of multiple small GTPases in vivo",
abstract = "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.",
author = "Jihoon Kim and Sangkyu Lee and Kanghoon Jung and Oh, {Won Chan} and Nury Kim and Seungkyu Son and Jo, {Young Ju} and Hyungbae Kwon and {Do Heo}, Won",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-018-08217-3",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Intensiometric biosensors visualize the activity of multiple small GTPases in vivo

AU - Kim, Jihoon

AU - Lee, Sangkyu

AU - Jung, Kanghoon

AU - Oh, Won Chan

AU - Kim, Nury

AU - Son, Seungkyu

AU - Jo, Young Ju

AU - Kwon, Hyungbae

AU - Do Heo, Won

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85060033766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060033766&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-08217-3

DO - 10.1038/s41467-018-08217-3

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 211

ER -