C. elegans sensory biology: G protein-coupled signal transduction and regulation
We use C. elegans sensory behavior (e.g. chemosensation) as a model to understand the interconnected mechanisms and regulatory pathways used by nerve cells to modulate signaling and ultimately control animal behavior. Areas of focus include: understanding how cGMP levels change in response to an animal’s feeding status and how cGMP moves through a gap junction neural circuit to modulate behavioral sensitivity to aversive stimuli; exploring the mechanisms by which the neurotransmitter dopamine modulates signaling and behavior; investigating how post-translational modification of G protein-coupled receptors (GPCRs) by arginine methylation regulates their function; and exploring how natural variation in chemosensory behavior is encoded and evolves at the molecular level.
The laboratories of Dr. Denise Ferkey and Dr. Michael Yu collaborated to provide the first direct evidence that GPCRs are functionally regulated by arginine methylation, focusing first on D2-like dopamine receptors. As reported in Science Signaling these GPCRs served as the founding members of a new class of proteins that are functionally regulated by arginine methylation. Their subsequent work has shown that additional GPCRs are also regulated by arginine methylation, delineating a new means of regulating G protein-coupled signal transduction. These findings have strong potential to influence the development of a new generation of treatments based on manipulating GPCR methylation status – not only for D2-linked neuropsychiatric disorders, but also for the treatment of diseases ranging from cancer to chronic heart failure.
Funding Support
Ellison Medical Foundation
National Science Foundation
National Institutes of Health

