G protein-regulated endocytic trafficking of adenylyl cyclase type 9
- UCSF, United States
- The University of Texas Health Science Center, United States
- UCSD, United States
- Tohoku University, Japan
Abstract
GPCRs are increasingly recognized to initiate signaling via heterotrimeric G proteins as they move through the endocytic network, but little is known about how relevant G protein effectors are localized. Here we report selective trafficking of adenylyl cyclase type 9 (AC9) from the plasma membrane to endosomes while adenylyl cyclase type 1 (AC1) remains in the plasma membrane, and stimulation of AC9 trafficking by ligand-induced activation of Gs-coupled GPCRs. AC9 transits a similar, dynamin-dependent early endocytic pathway as ligand-activated GPCRs. However, unlike GPCR traffic control which requires β-arrestin but not Gs, AC9 traffic control requires Gs but not β-arrestin. We also show that AC9, but not AC1, mediates cAMP production stimulated by endogenous receptor activation in endosomes. These results reveal dynamic and isoform-specific trafficking of adenylyl cyclase in the endocytic network, and a discrete role of a heterotrimeric G protein in regulating the subcellular distribution of a relevant effector.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided all main figures.
Article and author information
Author details
Funding
National Institutes of Health (DA010154,DA012864)
- Mark Von Zastrow
National Institutes of Health (GM60419)
- Carmen W Dessauer
National Institutes of Health (HL124049)
- Aparna B Sundaram
National Institutes of Health (CA209891)
- J Silvio Gutkind
National Institutes of Health (HL122508)
- Roshanak Irannejad
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Lazar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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G protein-regulated endocytic trafficking of adenylyl cyclase type 9
eLife 9:e58039.
https://doi.org/10.7554/eLife.58039
