Author ORCID Identifier
Yao - https://orcid.org/0000-0003-2706-2028
Deng - https://orcid.org/0000-0003-1556-1647
Wei - https://orcid.org/0000-0001-7682-9286
Gozem - https://orcid.org/0000-0002-6429-2853
Hamelberg - https://orcid.org/0000-0002-3785-3037
Yang -
Document Type
Article
Publication Date
8-26-2021
Publication Title
Angewandte Chemie International Edition
Volume
60
Issue
43
First Page
23289
Last Page
23298
DOI
https://doi.org/10.1002/anie.202108443
Abstract
Multi-scale calcium (Ca2+) dynamics, exhibiting wide-ranging temporal kinetics, constitutes a ubiquitous mode of signal transduction. We report a novel endoplasmic-reticulum (ER)-targeted Ca2+ indicator, R-CatchER, which showed superior kinetics in vitro (koff≥2×103 s−1, kon≥7×106 M−1 s−1) and in multiple cell types. R-CatchER captured spatiotemporal ER Ca2+ dynamics in neurons and hotspots at dendritic branchpoints, enabled the first report of ER Ca2+ oscillations mediated by calcium sensing receptors (CaSRs), and revealed ER Ca2+-based functional cooperativity of CaSR. We elucidate the mechanism of R-CatchER and propose a principle to rationally design genetically encoded Ca2+ indicators with a single Ca2+-binding site and fast kinetics by tuning rapid fluorescent-protein dynamics and the electrostatic potential around the chromophore. The design principle is supported by the development of G-CatchER2, an upgrade of our previous (G-)CatchER with improved dynamic range. Our work may facilitate protein design, visualizing Ca2+ dynamics, and drug discovery.
Recommended Citation
X. Deng, X.-Q. Yao, K. Berglund, B. Dong, D. Ouedraogo, M. A. Ghane, Y. Zhuo, C. McBean, Z. Z. Wei, S. Gozem, S. P. Yu, L. Wei, N. Fang, A. M. Mabb, G. Gadda, D. Hamelberg, J. J. Yang, Angew. Chem. Int. Ed. 2021, 60, 23289. https://doi.org/10.1002/anie.202108443
Comments
"This is the peer reviewed version of the following article: X. Deng, X.-Q. Yao, K. Berglund, B. Dong, D. Ouedraogo, M. A. Ghane, Y. Zhuo, C. McBean, Z. Z. Wei, S. Gozem, S. P. Yu, L. Wei, N. Fang, A. M. Mabb, G. Gadda, D. Hamelberg, J. J. Yang, Angew. Chem. Int. Ed. 2021, 60, 23289., which has been published in final form at [https://doi.org/10.1002/anie.202108443]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited."