G protein-regulated endocytic trafficking of adenylyl cyclase type 9

André M. Lazar, Roshanak Irannejad, Tanya A. Baldwin, Aparna B. Sundaram, J. Silvio Gutkind, Asuka Inoue, Carmen W. Dessauer, Mark Von Zastrow

Research output: Contribution to journalArticle

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 b-arrestin but not Gs, AC9 traffic control requires Gs but not b-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.

Original languageEnglish
Article numbere58039
Pages (from-to)1-24
Number of pages24
JournaleLife
Volume9
DOIs
Publication statusPublished - 2020 Jun

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Lazar, A. M., Irannejad, R., Baldwin, T. A., Sundaram, A. B., Gutkind, J. S., Inoue, A., Dessauer, C. W., & Zastrow, M. V. (2020). G protein-regulated endocytic trafficking of adenylyl cyclase type 9. eLife, 9, 1-24. [e58039]. https://doi.org/10.7554/eLife.58039