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, Hyung Bae 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

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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., Jo, Y. J., Kwon, H. B., & 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