Reference - Detail
| RRC ID | 86732 |
|---|---|
| Author | Herdt L, Schihada H, Kurz M, Ernst S, Eberlein J, Kolb P, Krasel C, Bünemann M, Helker CSM. |
| Title | In vivo measurement of an Apelin gradient with a genetically encoded APLNR conformation biosensor. |
| Journal | Nat Commun |
| Abstract |
The Apelin receptor (APLNR), a class A G-protein coupled receptor, plays a crucial role during cardiovascular development and tumor angiogenesis. To understand its spatiotemporal activity in health and disease is fundamental for the development of drugs to manipulate its activation state. To obtain this understanding, here we develop a tool box of various APLNR conformation biosensors, based on FRET, BRET and the conformation-sensitive fluorophore circularly permuted GFP (cpGFP), with further focus on its in vivo application. We demonstrate the functionality of our biosensors by pharmacological characterization and signal transduction analysis in vitro. Two APLNR-cpGFP biosensors show superior signal-to-noise ratio and are further analyzed for their in vivo applicability. In zebrafish embryos, APLNR-cpGFP biosensors are able to bind both endogenous ligands, Apelin and Apela, and visualize endogenous Aplnr activity in growing blood vessels. Moreover, we are able to measure an Apelin ligand gradient across cellular distances in vivo. Hence, these APLNR conformation biosensors are powerful tools to resolve the spatiotemporal Apelin signaling activity in health and disease. |
| Volume | 16(1) |
| Pages | 6682 |
| Published | 2025-7-21 |
| DOI | 10.1038/s41467-025-61781-3 |
| PII | 10.1038/s41467-025-61781-3 |
| PMID | 40691309 |
| PMC | PMC12280157 |
| MeSH | Animals Apelin* / metabolism Apelin Receptors* / chemistry Apelin Receptors* / genetics Apelin Receptors* / metabolism Biosensing Techniques* / methods Embryo, Nonmammalian / metabolism Fluorescence Resonance Energy Transfer Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism HEK293 Cells Humans Ligands Protein Conformation Receptors, G-Protein-Coupled* / genetics Receptors, G-Protein-Coupled* / metabolism Signal Transduction Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Zebrafish | UAS:RFP |