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Subcellular compartment determines signal dominance: Endosomal cAMP overrides concurrent plasma membrane RhoA activation from a single receptor.
Proceedings of the National Academy of Sciences · · Journal Article
Savransky, Pacheco + more
Abstract ↗AI summary
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Endosomal cAMP generated by activated GPR64/ADGRG2 overrides concurrent plasma membrane G13/RhoA activation, producing net RhoA inactivation.
- Why it matters: It was unclear how spatially distinct signals from one activated GPCR compete to set the final cellular response.
- What they did: Using GPR64/ADGRG2 as a model, ligand activation triggered plasma membrane G13/RhoA and endosome-persistent Gs/cAMP after internalization; blocking endocytosis or endosomal Gs reversed the outcome.
- The result: In parathyroid cells, endosomal signal dominance suppressed parathyroid hormone secretion independently of extracellular Ca2+ levels, supporting compartment-based control of GPCR signaling.
The findingWhy it mattersWhat they didThe result
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