Engineering of NEMO As Calcium Indicators with Large Dynamics and High Sensitivity

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2023 Apr 20

PMID 37081094

Authors

Jia Li

Ziwei Shang

Jia-Hui Chen

Wenjia Gu

Li Yao

Xin Yang

Xiaowen Sun

Liuqing Wang

Tianlu Wang

Siyao Liu

Jiajing Li

Tingting Hou

Dajun Xing

Donald L Gill

Jiejie Li

Shi-Qiang Wang

Lijuan Hou

Yubin Zhou

Ai-Hui Tang

Xiaohui Zhang

Youjun Wang

Affiliations

Soon will be listed here.

Abstract

Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca-modulated physiological processes in both mammals and plants.

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