PMID- 37081094
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20231116
IS  - 1548-7105 (Electronic)
IS  - 1548-7091 (Print)
IS  - 1548-7091 (Linking)
VI  - 20
IP  - 6
DP  - 2023 Jun
TI  - Engineering of NEMO as calcium indicators with large dynamics and high 
      sensitivity.
PG  - 918-924
LID - 10.1038/s41592-023-01852-9 [doi]
AB  - 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(2+) 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(2+) 
      signals, NEMO sensors may find broad applications in monitoring neuronal 
      activities and other Ca(2+)-modulated physiological processes in both mammals and 
      plants.
CI  - (c) 2023. The Author(s).
FAU - Li, Jia
AU  - Li J
AUID- ORCID: 0000-0003-1274-3867
AD  - Beijing Key Laboratory of Gene Resource and Molecular Development, College of 
      Life Sciences, Beijing Normal University, Beijing, China.
FAU - Shang, Ziwei
AU  - Shang Z
AD  - State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern 
      Institute for Brain Research, Beijing Normal University, Beijing, China.
FAU - Chen, Jia-Hui
AU  - Chen JH
AD  - Hefei National Research Center for Physical Sciences at the Microscale, CAS Key 
      Laboratory of Brain Function and Disease, and Ministry of Education Key 
      Laboratory for Membraneless Organelles and Cellular Dynamics, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China.
FAU - Gu, Wenjia
AU  - Gu W
AD  - Beijing Key Laboratory of Gene Resource and Molecular Development, College of 
      Life Sciences, Beijing Normal University, Beijing, China.
FAU - Yao, Li
AU  - Yao L
AD  - State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern 
      Institute for Brain Research, Beijing Normal University, Beijing, China.
FAU - Yang, Xin
AU  - Yang X
AD  - Exercise Physiology and Neurobiology Laboratory, College of PE and Sports, 
      Beijing Normal University, Beijing, China.
FAU - Sun, Xiaowen
AU  - Sun X
AD  - State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern 
      Institute for Brain Research, Beijing Normal University, Beijing, China.
FAU - Wang, Liuqing
AU  - Wang L
AD  - Beijing Key Laboratory of Gene Resource and Molecular Development, College of 
      Life Sciences, Beijing Normal University, Beijing, China.
FAU - Wang, Tianlu
AU  - Wang T
AD  - Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
FAU - Liu, Siyao
AU  - Liu S
AD  - Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
FAU - Li, Jiajing
AU  - Li J
AD  - Beijing Key Laboratory of Gene Resource and Molecular Development, College of 
      Life Sciences, Beijing Normal University, Beijing, China.
FAU - Hou, Tingting
AU  - Hou T
AD  - State Key Laboratory of Membrane Biology College of Life Sciences, Peking 
      University, Beijing, China.
FAU - Xing, Dajun
AU  - Xing D
AUID- ORCID: 0000-0002-6953-1198
AD  - State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern 
      Institute for Brain Research, Beijing Normal University, Beijing, China.
FAU - Gill, Donald L
AU  - Gill DL
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, PA, USA.
FAU - Li, Jiejie
AU  - Li J
AD  - Beijing Key Laboratory of Gene Resource and Molecular Development, College of 
      Life Sciences, Beijing Normal University, Beijing, China.
FAU - Wang, Shi-Qiang
AU  - Wang SQ
AD  - State Key Laboratory of Membrane Biology College of Life Sciences, Peking 
      University, Beijing, China.
FAU - Hou, Lijuan
AU  - Hou L
AD  - Exercise Physiology and Neurobiology Laboratory, College of PE and Sports, 
      Beijing Normal University, Beijing, China.
FAU - Zhou, Yubin
AU  - Zhou Y
AD  - Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA. 
      yubinzhou@tamu.edu.
AD  - Department of Translational Medical Sciences, School of Medicine, Texas A&M 
      University, Houston, TX, USA. yubinzhou@tamu.edu.
FAU - Tang, Ai-Hui
AU  - Tang AH
AD  - Hefei National Research Center for Physical Sciences at the Microscale, CAS Key 
      Laboratory of Brain Function and Disease, and Ministry of Education Key 
      Laboratory for Membraneless Organelles and Cellular Dynamics, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China. tangah@ustc.edu.cn.
AD  - Institute of Artificial Intelligence, Hefei Comprehensive National Science 
      Center, Hefei, China. tangah@ustc.edu.cn.
FAU - Zhang, Xiaohui
AU  - Zhang X
AD  - State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern 
      Institute for Brain Research, Beijing Normal University, Beijing, China. 
      xhzhang@bnu.edu.cn.
FAU - Wang, Youjun
AU  - Wang Y
AUID- ORCID: 0000-0003-0961-1716
AD  - Beijing Key Laboratory of Gene Resource and Molecular Development, College of 
      Life Sciences, Beijing Normal University, Beijing, China. wyoujun@bnu.edu.cn.
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China. 
      wyoujun@bnu.edu.cn.
LA  - eng
GR  - 2019YFA0802104/Chinese Ministry of Science and Technology | Department of S and T 
      for Social Development (Department of S&T for Social Development)/
GR  - 92254301/National Natural Science Foundation of China (National Science 
      Foundation of China)/
GR  - 91954205/National Natural Science Foundation of China (National Science 
      Foundation of China)/
GR  - 32171033/National Natural Science Foundation of China (National Science 
      Foundation of China)/
GR  - 2021M703089/China Postdoctoral Science Foundation)/
PT  - Journal Article
DEP - 20230420
PL  - United States
TA  - Nat Methods
JT  - Nature methods
JID - 101215604
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Indicators and Reagents)
SB  - IM
MH  - Animals
MH  - *Calcium/metabolism
MH  - *Neurons/physiology
MH  - Calcium Signaling/physiology
MH  - Indicators and Reagents
MH  - Mammals/metabolism
PMC - PMC10250196
COIS- The authors declare no competing interests.
EDAT- 2023/04/21 00:42
MHDA- 2023/06/12 06:42
PMCR- 2023/04/20
CRDT- 2023/04/20 23:22
PHST- 2022/06/07 00:00 [received]
PHST- 2023/03/16 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/04/21 00:42 [pubmed]
PHST- 2023/04/20 23:22 [entrez]
PHST- 2023/04/20 00:00 [pmc-release]
AID - 10.1038/s41592-023-01852-9 [pii]
AID - 1852 [pii]
AID - 10.1038/s41592-023-01852-9 [doi]
PST - ppublish
SO  - Nat Methods. 2023 Jun;20(6):918-924. doi: 10.1038/s41592-023-01852-9. Epub 2023 
      Apr 20.