Intensiometric Biosensors Visualize the Activity of Multiple Small GTPases in Vivo

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jan 16

PMID 30643148

Citations 27

Authors

Jihoon Kim

Sangkyu Lee

Kanghoon Jung

Won Chan Oh

Nury Kim

Seungkyu Son

YoungJu Jo

Hyung-Bae Kwon

Won Do Heo

Affiliations

Soon will be listed here.

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.

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