Engineering of NEMO as calcium indicators with large dynamics and high sensitivity. Academic Article uri icon


  • 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.

published proceedings

  • Nat Methods

altmetric score

  • 66.08

author list (cited authors)

  • Li, J., Shang, Z., Chen, J., Gu, W., Yao, L. i., Yang, X., ... Wang, Y.

citation count

  • 2

complete list of authors

  • Li, Jia||Shang, Ziwei||Chen, Jia-Hui||Gu, Wenjia||Yao, Li||Yang, Xin||Sun, Xiaowen||Wang, Liuqing||Wang, Tianlu||Liu, Siyao||Li, Jiajing||Hou, Tingting||Xing, Dajun||Gill, Donald L||Li, Jiejie||Wang, Shi-Qiang||Hou, Lijuan||Zhou, Yubin||Tang, Ai-Hui||Zhang, Xiaohui||Wang, Youjun

publication date

  • June 2023