The Garcia-Marcos Lab has recently published a study in Molecular Cell (https://doi.org/10.1016/j.molcel.2023.06.006; prepint in: https://www.biorxiv.org/content/10.1101/2023.03.03.529094v1) titled “Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G protein subunits”. The paper describes how different signaling responses triggered by the same neurotransmitter receptor must be carefully scaled to ensure proper brain function. They found that the protein named GINIP shifts the balance of two different G protein sub-species activated simultaneously by G protein-coupled receptors (GPCRs), a large family of surface receptors that respond many neurotransmitters and neuropeptides, including GABA, dopamine, serotonin, or opioids. This mechanism operates in synapses that dampen neurotransmission and, when disabled, results in increased seizure susceptibility in mouse models. These findings have important implications for the fundamental understanding of neuronal communication and for the development of new therapeutic agents that act on GPCRs.
This work was co-led by Jong-Chan Park (Postdoc) and Alex Luebbers (Graduate Student) with collaborations from the Martemyanov Lab at UF Scripps Biomedical Research Institute and the Yano Lab at Northeastern University, and has been highlighted by Molecular Cell (https://doi.org/10.1016/j.molcel.2023.06.034) and Science Signaling (https://www.science.org/doi/10.1126/scisignal.adj6131).