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bioRxiv · 10.1101/2020.04.23.057026

G protein-regulated endocytic trafficking of adenylyl cyclase type 9

Lazar, A. M.·Irannejad, R.·Baldwin, T. A.·Sundaram, A. B.·Gutkind, J. S.·Inoue, A.·Dessauer, C. W.·Von Zastrow, M.
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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 dynamic 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 or Gs. AC9 transits a similar dynamin-dependent early endocytic pathway as activated GPCRs but, in contrast to GPCR trafficking which is regulated by {beta}-arrestin but not Gs, AC9 trafficking is regulated by Gs but not {beta}-arrestin. We also show that AC9, but not AC1, contributes to cAMP production from 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 controlling subcellular location of a relevant effector.

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Lazar, A. M., Irannejad, R., Baldwin, T. A., Sundaram, A. B., Gutkind, J. S., Inoue, A., Dessauer, C. W., Von Zastrow, M.. 2020-04-25. G protein-regulated endocytic trafficking of adenylyl cyclase type 9. https://doi.org/10.1101/2020.04.23.057026

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