The role of GQ localization in gpcr signal diversification

Active Project Grant Awarded Last action

Award ID
F32GM165113
Recipient
Awarding agency
Obligated
$80,800

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 0% complete
Place of performance
San Francisco, CA 94143, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Cells of multicellular organisms must sense a dizzying array of chemical signals, both from the environment and one another. To do this, they rely on over 800 G protein-coupled receptors (GPCRS), which propagate signals through just four primary G protein pathways. This creates a major bottleneck: how do cells discriminate dozens of chemical messages when they converge on the same G protein? One way cells can encode additional diversity is by regulating the timing or subcellular location of G protein activity. A decade of work shows that GPCRS can activate G proteins at endosomes - the first organelle GPCRS encounter after activation-induced internalization. For the GS family, this endosomal activity is now known to relay unique signals when compared to canonical signaling at the plasma membrane. I aim to expand this understanding of compartmentalized signaling to the GQ subfamily, which regulates intracellular calcium release downstream of dozens of receptors and across nearly all organ systems. However, this canonical calcium pathway is unlikely to function at endosomes, where its essential substrate PIP2 is scarce. Therefore, this project will test the hypothesis that GQ encodes unique cellular signaling programs on endosomes. Using new biosensors that detect active G proteins at native levels with high spatial precision, I will define how cells encode, propagate, and respond GQ signals in endosomes. First, I will map endosomal GQ activity across GPCRS with divergent internalization profiles to understand how receptor trafficking directs endosomal signaling. Next, I will develop subcellular proximity labeling probes to identify the unique effectors of GQ in endosomes. Finally, I will convert biosensors into compartment-specific inhibitors to dissect the roles of endosomal GQ in global cellular responses. Understanding this new layer of receptor regulation for the GQ pathway will reveal how cells spatially organize signal transduction to interpret a myriad of endogenous and therapeutic stimuli. My training plan will build my theoretical and experimental toolkit in cell biology, preparing me for an independent career linking molecular mechanisms of receptor function to the cellular outputs they drive.

Quick answers

Who received award F32GM165113?

F32GM165113 was awarded to The Regents Of The University Of California. San Francisco by National Institute of General Medical Sciences (National Institutes of Health) on November 25, 2026.

How much is award F32GM165113 worth?

$80,800 has been obligated on F32GM165113.

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