Engineering of NEMO as calcium indicators with large dynamics and high sensitivity
Abstract Genetically-encoded calcium indicators (GECI) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of sub-optimal 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 ~20-fold larger than the top-of-the-range GCaMP series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared to GCaMPs, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times largerin 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..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Jia [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| doi: |
10.1101/2022.08.23.504677 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI036967181 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI036967181 | ||
| 003 | DE-627 | ||
| 005 | 20240424104856.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220827s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2022.08.23.504677 |2 doi | |
| 035 | |a (DE-627)XBI036967181 | ||
| 035 | |a (biorXiv)10.1101/2022.08.23.504677 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Jia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Engineering of NEMO as calcium indicators with large dynamics and high sensitivity |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Genetically-encoded calcium indicators (GECI) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of sub-optimal 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 ~20-fold larger than the top-of-the-range GCaMP series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared to GCaMPs, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times largerin 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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Shang, Ziwei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jia-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Wenjia |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xiaowen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Liuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tianlu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Siyao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiajing |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Dajun |e verfasserin |4 aut | |
| 700 | 1 | |a Gill, Donald L. |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiejie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shi-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Lijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yubin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Ai-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youjun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2024) vom: 23. Apr. |
| 773 | 1 | 8 | |g year:2024 |g day:23 |g month:04 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41592-023-01852-9 |x 0 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2022.08.23.504677 |x 0 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 23 |c 04 | ||