Engineering of NEMO as calcium indicators with large dynamics and high sensitivity

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 ZhangYoujun Wang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 Ca2+ 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 Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.

Original languageEnglish (US)
Pages (from-to)918-924
Number of pages7
JournalNature methods
Volume20
Issue number6
DOIs
StatePublished - Jun 2023

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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