NEW PUBLICATION BY THE GARCIA-MARCOS LAB
A recent publication in Nature Chemical Biology (https://www.nature.com/articles/s41589-025-02138-1) led by Jingyi Zhao in the Garcia-Marcos Lab describes the discovery and optimization of broadly applicable genetically-encoded probes and peptide-based compounds specifically inhibit Gαs, the prototypical signal transducer of G protein-coupled receptors (GPCRs). These tools were leveraged to provide new mechanistic insights into GPCR signaling at the subcellular scale by revealing definitive evidence for G protein signaling at endosomes. The newly developed peptide-based compound named α-sintide allowed the inhibition signaling in multiple contexts: blocking an oncogenic G protein mutant, inhibiting heart cell responses to adrenaline, or preventing T cell exhaustion.
This work was done in collaboration with the Varelas Lab in our Department and with the Irannejad Lab and Vilardaga Lab at UCSF and U of Pittsburgh, respectively.