The Garcia-Marcos Lab has recently published a study in Molecular Cell titled, “Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G protein subunits.” 

The paper describes how various 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 to many neurotransmitters and neuropeptides (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 and Science Signaling.

Click here to read the full article.

Garcia-Marcos Lab
GINIP localizes to inhibitory but not excitatory synapses. GINIP protein localizes to dendritic puncta in cortical neurons. DIV21 cortical neurons from GINIP +/+ or 1a/1a mice were co-stained for GINIP and synaptophysin (SYP) before fluorescence imaging. Yellow boxes indicate areas enlarged on the right side of the main images. Enlarged views of representative neurites (yellow box) are shown on the right side of the main images (Figure 6. Park et al., 2023).