Intracellular GPCR Signaling: Cell Biology, Pharmacology and Physiology
Tuesday April 27, 2021
Eastern Time (ET)
View session on the EB Virtual Platform (EB registration required)
Medical College of Wisconsin
GPCRs and their downstream signaling cascades control all essential physiology and accordingly are targeted by close to half of the current drugs on the market. It is now clear that many GPCRs generate a discrete "second wave" of G protein-dependent signaling from internal organelles. Moreover, we are beginning to appreciate that active GPCRs in different compartments can give rise to functionally distinct cellular responses, which in turn could underlie unique physiologies and selective drug actions. This Symposium will feature both established and emerging new leaders in the study of intracellular GPCR signaling whose research collectively spans questions from basic cell biological and molecular mechanisms to physiology and pathophysiology.
- Duke University
Mechanistic and Functional Dissection of Spatially Encoded GPCR Signaling
We have demonstrated that GPCR/G protein activation in different compartments can lead to functionally distinct responses by linking receptor signaling at the endosome to the activation of transcriptional responses. We will discuss our most recent work on developing and applying unbiased genomic and functional genomics platforms to dissect the mechanisms and consequences of spatially biased receptor activity.
- Washington University
Intracellular mGlu5 Receptors Play a Key Role in Vivo
Dr. O’Malley’s group has shown that the majority of metabotropic glutamate receptors are located on nuclear and ER membranes of neurons, and that intracellular receptors play key roles in mGluR5-dependent Ca2+ release and long-term depression of excitatory synaptic strength. Dr. O’Malley will discuss recent progress made in developing mouse models of strictly cell surface or intracellular mGluRs to study the in vivo relevance of GPCR compartmentalization.
- University of Michigan
GPCRs/G Proteins and Golgi Localized Lipid Signaling in Cardiac Physiology
Dr. Smrcka has demonstrated that both Gβγ and Golgi localized β1-adrenergic receptors/cAMP activate perinuclear PLCε to generate diacylglycerol (DAG) from PI4P. Importantly, he has shown that genetic or pharmacological manipulation of these Golgi localized cascades prevents development of cardiac hypertrophy. Dr. Smrcka will discuss and elaborate on these recent recent findings.
- Medical College of Wisconsin
GPCR Regulation of Survival Signaling from Endosomes
Our recent research has shown that GPCR signaling from endosomes is linked to anchorage independent cell survival. This is particularly relevant to the metastatic spread of cancer that is associated with a class of GPCRs known as chemokine receptors. We will discuss recent developments on the unexpected role of ubiquitin on the activation of factors that mediate survival signaling from endosomes.