Probing PAC1 receptor activation across species with an engineered sensor

Cola, Reto B; Niethammer, Salome N; Rajamannar, Preethi; Gresch, Andrea; Bhat, Musadiq A; Assoumou, Kevin; Williams, Elyse T; Hauck, Patrick; Hartrampf, Nina; Benke, Dietmar; Stoeber, Miriam; Levkowitz, Gil; Melzer, Sarah; Patriarchi, Tommaso

doi:10.7554/eLife.96496

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Cola, R. B., Niethammer, S. N., Rajamannar, P., Gresch, A., Bhat, M. A., Assoumou, K., Williams, E. T., Hauck, P., Hartrampf, N., Benke, D., Stoeber, M., Levkowitz, G., Melzer, S., & Patriarchi, T. (2024). Probing PAC1 receptor activation across species with an engineered sensor. ELife, 13, RP96496. https://doi.org/10.7554/eLife.96496

Abstract

Class-B1 G-protein-coupled receptors (GPCRs) are an important family of clinically relevant drug targets that remain difficult to investigate via high-throughput screening and in animal models. Here, we engineered PAClight1${P78A}$, a novel genetically encoded sensor based on a class-B1 GPCR (the human PAC1 receptor, hmPAC1R) endowed with high dynamic range (ΔF/F${0}$ = 1100%), excellent ligand selectivity, and rapid activation kinetics (τ$_{ON}$