@article{5b1108fb99d649e79353b5cc4085a71c,
title = "G protein-regulated endocytic trafficking of adenylyl cyclase type 9",
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.",
author = "Lazar, {Andr{\'e} M.} and Roshanak Irannejad and Baldwin, {Tanya A.} and Sundaram, {Aparna B.} and Gutkind, {J. Silvio} and Asuka Inoue and Dessauer, {Carmen W.} and Zastrow, {Mark Von}",
note = "Funding Information: We thank B Lobingier, G Peng, L Ripoll, M Stoeber and other current and past members of the von Zastrow laboratory for advice and critical discussions. We thank R D Mullins, R Sunahara and J Taun- ton for valuable discussion and suggestions. We thank M Soto-Velasquez and V Watts for valuable discussion and the generous gift of AC3/6 knockout cells. We thank the E Roth group for their gen- erous support and lab equipment, and K Kurtz for assistance. This work was supported by grantsfrom the US National Institutes of Health (DA010711 and DA012864 to MvZ; GM60419 to CWD; HL124049 to AAS; CA209891 to JSG). AL is an ARCS scholar. Funding Information: We thank B Lobingier, G Peng, L Ripoll, M Stoeber and other current and past members of the von Zastrow laboratory for advice and critical discussions. We thank R D Mullins, R Sunahara and J Taun-ton for valuable discussion and suggestions. We thank M Soto-Velasquez and V Watts for valuable discussion and the generous gift of AC3/6 knockout cells. We thank the E Roth group for their generous support and lab equipment, and K Kurtz for assistance. This work was supported by grants from the US National Institutes of Health (DA010711 and DA012864 to MvZ; GM60419 to CWD; HL124049 to AAS; CA209891 to JSG). AL is an ARCS scholar.",
year = "2020",
month = jun,
doi = "10.7554/eLife.58039",
language = "English",
volume = "9",
pages = "1--24",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}