Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells
Abstract The Endoplasmic/sarcoplasmic reticulum (ER/SR) is central to calcium (Ca2+) signaling, yet current genetically encoded Ca2+ indicators (GECIs) cannot detect elementary Ca2+ release events from ER/SR, particularly in muscle cells. Here, we report NEMOer, a set of organellar GECIs, to efficie...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58705-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850202675767934976 |
|---|---|
| author | Wenjia Gu Jia-Hui Chen Yiyin Zhang Zhirong Wang Jia Li Sijia Wang Hanhan Zhang Amin Jiang Ziyi Zhong Jiaxuan Zhang Ze Xu Panpan Liu Chao Xi Tingting Hou Donald L. Gill Dong Li Yu Mu Shi-Qiang Wang Ai-Hui Tang Youjun Wang |
| author_facet | Wenjia Gu Jia-Hui Chen Yiyin Zhang Zhirong Wang Jia Li Sijia Wang Hanhan Zhang Amin Jiang Ziyi Zhong Jiaxuan Zhang Ze Xu Panpan Liu Chao Xi Tingting Hou Donald L. Gill Dong Li Yu Mu Shi-Qiang Wang Ai-Hui Tang Youjun Wang |
| author_sort | Wenjia Gu |
| collection | DOAJ |
| description | Abstract The Endoplasmic/sarcoplasmic reticulum (ER/SR) is central to calcium (Ca2+) signaling, yet current genetically encoded Ca2+ indicators (GECIs) cannot detect elementary Ca2+ release events from ER/SR, particularly in muscle cells. Here, we report NEMOer, a set of organellar GECIs, to efficiently capture ER Ca2+ dynamics with increased sensitivity and responsiveness. NEMOer indicators exhibit dynamic ranges an order of magnitude larger than G-CEPIA1er, enabling 2.7-fold more sensitive detection of Ca2+ transients in both non-excitable and excitable cells. The ratiometric version further allows super-resolution monitoring of local ER Ca2+ homeostasis and dynamics. Notably, NEMOer-f enabled the inaugural detection of Ca2+ blinks, elementary Ca2+ releasing signals from the SR of cardiomyocytes, as well as in vivo spontaneous SR Ca2+ releases in zebrafish. In summary, the highly dynamic NEMOer sensors expand the repertoire of organellar Ca2+ sensors that allow real-time monitoring of intricate Ca2+ dynamics and homeostasis in live cells with high spatiotemporal resolution. |
| format | Article |
| id | doaj-art-dac6bfe4fd3b4d2a9dcfad7a1631a0e2 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dac6bfe4fd3b4d2a9dcfad7a1631a0e22025-08-20T02:11:42ZengNature PortfolioNature Communications2041-17232025-04-0116111210.1038/s41467-025-58705-6Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cellsWenjia Gu0Jia-Hui Chen1Yiyin Zhang2Zhirong Wang3Jia Li4Sijia Wang5Hanhan Zhang6Amin Jiang7Ziyi Zhong8Jiaxuan Zhang9Ze Xu10Panpan Liu11Chao Xi12Tingting Hou13Donald L. Gill14Dong Li15Yu Mu16Shi-Qiang Wang17Ai-Hui Tang18Youjun Wang19Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityDepartment of Anatomy, School of Basic Medicine, Anhui Medical UniversityState Key Laboratory of Membrane Biology, College of Life Sciences, Peking UniversityInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityState Key Laboratory of Membrane Biology, College of Life Sciences, Peking UniversityBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityState Key Laboratory of Membrane Biology, College of Life Sciences, Peking UniversityDepartment of Cellular and Molecular Physiology, Pennsylvania State University College of MedicineNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesState Key Laboratory of Membrane Biology, College of Life Sciences, Peking UniversityAnhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science CenterBeijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal UniversityAbstract The Endoplasmic/sarcoplasmic reticulum (ER/SR) is central to calcium (Ca2+) signaling, yet current genetically encoded Ca2+ indicators (GECIs) cannot detect elementary Ca2+ release events from ER/SR, particularly in muscle cells. Here, we report NEMOer, a set of organellar GECIs, to efficiently capture ER Ca2+ dynamics with increased sensitivity and responsiveness. NEMOer indicators exhibit dynamic ranges an order of magnitude larger than G-CEPIA1er, enabling 2.7-fold more sensitive detection of Ca2+ transients in both non-excitable and excitable cells. The ratiometric version further allows super-resolution monitoring of local ER Ca2+ homeostasis and dynamics. Notably, NEMOer-f enabled the inaugural detection of Ca2+ blinks, elementary Ca2+ releasing signals from the SR of cardiomyocytes, as well as in vivo spontaneous SR Ca2+ releases in zebrafish. In summary, the highly dynamic NEMOer sensors expand the repertoire of organellar Ca2+ sensors that allow real-time monitoring of intricate Ca2+ dynamics and homeostasis in live cells with high spatiotemporal resolution.https://doi.org/10.1038/s41467-025-58705-6 |
| spellingShingle | Wenjia Gu Jia-Hui Chen Yiyin Zhang Zhirong Wang Jia Li Sijia Wang Hanhan Zhang Amin Jiang Ziyi Zhong Jiaxuan Zhang Ze Xu Panpan Liu Chao Xi Tingting Hou Donald L. Gill Dong Li Yu Mu Shi-Qiang Wang Ai-Hui Tang Youjun Wang Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells Nature Communications |
| title | Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells |
| title_full | Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells |
| title_fullStr | Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells |
| title_full_unstemmed | Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells |
| title_short | Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells |
| title_sort | highly dynamic and sensitive nemoer calcium indicators for imaging er calcium signals in excitable cells |
| url | https://doi.org/10.1038/s41467-025-58705-6 |
| work_keys_str_mv | AT wenjiagu highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT jiahuichen highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT yiyinzhang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT zhirongwang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT jiali highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT sijiawang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT hanhanzhang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT aminjiang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT ziyizhong highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT jiaxuanzhang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT zexu highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT panpanliu highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT chaoxi highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT tingtinghou highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT donaldlgill highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT dongli highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT yumu highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT shiqiangwang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT aihuitang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells AT youjunwang highlydynamicandsensitivenemoercalciumindicatorsforimagingercalciumsignalsinexcitablecells |