G protein-regulated endocytic trafficking of adenylyl cyclase type 9.

ELife
André M LazarMark Von Zastrow

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.

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Citations

Sep 12, 2020·Biochemical Society Transactions·Harrison M YorkSenthil Arumugam
Nov 25, 2020·The Journal of Membrane Biology·Stephanie E Crilly, Manojkumar A Puthenveedu
Dec 19, 2020·Pharmacological Reviews·Manuela ZaccoloMiguel J Lobo
Oct 15, 2020·PLoS Genetics·Khairunnisa Mentari SemestaNikoleta G Tsvetanova
Feb 20, 2021·The FEBS Journal·Anthony H Nguyen, Robert J Lefkowitz
Mar 3, 2021·Nature Chemical Biology·Grace E PengMark von Zastrow
May 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Shane C WrightMichel Bouvier
Jun 3, 2021·Nature Reviews. Molecular Cell Biology·Sara SigismundPier Paolo Di Fiore
Feb 20, 2021·Annual Review of Biochemistry·Mark von Zastrow, Alexander Sorkin
Aug 27, 2021·The Journal of Biological Chemistry·Jean-Pierre VilardagaKarina A Peña
Oct 27, 2021·Physiological Reviews·Katrina F OstromRennolds S Ostrom

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Methods Mentioned

BETA
ELISA
confocal microscopy
GTPase
environmental stress
biosensors
biosensor
biopsy

Software Mentioned

Prism GraphPad
ParticleTracker ImageJ
MATLAB
Micro
Excel
ImageJ
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