András Tóth

I am so happy that our paper on the spatiotemporal bias in beta-arrestin signaling is finally out in @scisignal! In this short tweetorial, I would like to sum up the main findings. 🧵doi.org/10.1126/scisig…

I am delighted to report that our latest paper has now been published in Science Advances: science.org/doi/10.1126/sc… In this study, we generated and characterised a humanised GLP‑1R mouse model carrying the gain‑of‑function A316T variant using CRISPR/Cas9 knock‑in technology.

Hooray!! The first major product from the lab is out today @Nature. Small molecules that bind the GPCR-transducer interface change G protein subtype selectivity in predictable ways, enabling rational drug design.💥 Check it out! 👉nature.com/articles/s4158… 🧵👇

Our latest review in Eur J Pharm Sci summarizes recent advances (2018–2024) in #fluorescent probe development for Class A #GPCRs, analyzing over 120 newly developed probes covering 60 GPCRs. doi.org/10.1016/j.ejps…

Our new photoaffinity labelling technology (bit.ly/4kiVZ74) is published in @angew_chem. It is more biocompatible, more efficienct, cheaper and easily accessible, even as a late-stage modification. We are working with @EnamineLtd to make it available for the community.

We are depositing the following mice to @MMRRC Adgrf5-EGFP-CT-IRES-CRE GPR123- EGFP-CT-IRES-CRE GPR124- EGFP-CT-IRES-CRE GPR125- EGFP-CT-IRES-CRE Gpr133-EGFP-CT-IRES-CRE GPR156-IRES-Cre GPR156-mGL-IRES-Cre GPR75-IRES-Cre Bai1 mGL-CT-IRES-Cre GPRC5A- EGFP-CT-IRES-ERT2-CRE 1/2

Delighted to share our study on promiscuous chemokine binding at a chemokine receptor, now published in @MolecularCell!!! Molecular basis of promiscuous chemokine binding and structural mimicry at the C-X-C chemokine receptor, CXCR2: Molecular Cell cell.com/molecular-cell…

Receptors are essential for cell communication, yet most comp CCC tools focus on ligand/receptor expression, not receptor activity. To address this, we developed RIDDEN, a model that infers activity for 229 receptors from transcriptomics data. 1/ n biorxiv.org/content/10.110… 1/n

Our perspectives on the various aspects of bias in GPCR function, with a special focus on their relevance to the kidney, have been published in @NatRevNeph. nature.com/articles/s4158…

@ben_szalai We hope that the improved understanding of biased signaling will aid in the development of better biased compounds.

To get a broader picture, @ben_szalai built an ODE-based mathematical model. This model verified the role of ligand k_off and revealed that compartment-specific differences in GPCR phosphorylation/dephosphorylation are crucial for ligand k_off effects to emerge.

Astonishingly, differences in beta-arrestin recruitment almost completely disappeared without endocytosis. Since beta-arrestins form stable interaction with AT1R, even at endosomes, we speculated that agonist-specific differences occur endosomally.

Why is that so? Since differences in agonist effects developed over a relatively long time, we hypothesized that receptor endocytosis might account for it. We then checked what happens in the absence of endocytosis.

I am so happy that our paper on the spatiotemporal bias in beta-arrestin signaling is finally out in @scisignal! In this short tweetorial, I would like to sum up the main findings. 🧵doi.org/10.1126/scisig…

We measured the transducer activation profile of various AT1 angiotensin receptor agonists in real time with BRET sensors. We found substantial temporal variance in agonist effects for beta-arrestin recruitment but not for G protein activation.

A new paper shows that the #endocytosis of #GPCRs such as AT1R can influence biased signaling through #BetaArrestin, suggesting the efficacy of beta-arrestin-binding ligands depends on spatial location as much as on receptor conformation. @semmelweishu scim.ag/7th