1. Cell Biology

G protein-regulated endocytic trafficking of adenylyl cyclase type 9

  1. André M Lazar
  2. Roshanak Irannejad
  3. Tanya A Baldwin
  4. Aparna B Sundaram
  5. J Silvio Gutkind
  6. Asuka Inoue
  7. Carmen W Dessauer
  8. Mark Von Zastrow  Is a corresponding author
  1. UCSF, United States
  2. The University of Texas Health Science Center, United States
  3. UCSD, United States
  4. Tohoku University, Japan
https://doi.org/10.7554/eLife.58039
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Cite this article
  1. André M Lazar
  2. Roshanak Irannejad
  3. Tanya A Baldwin
  4. Aparna B Sundaram
  5. J Silvio Gutkind
  6. Asuka Inoue
  7. Carmen W Dessauer
  8. Mark Von Zastrow
(2020)
G protein-regulated endocytic trafficking of adenylyl cyclase type 9
eLife 9:e58039.
https://doi.org/10.7554/eLife.58039
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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 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

  1. André M Lazar

    Biochemistry & Biophysics, UCSF, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Roshanak Irannejad

    Biochemistry & Biophysics, UCSF, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Tanya A Baldwin

    Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Aparna B Sundaram

    Medicine, UCSF, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4076-4756

  5. J Silvio Gutkind

    Pharmacology, UCSD, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Asuka Inoue

    Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    Competing interests
    The authors declare that no competing interests exist.

  7. Carmen W Dessauer

    Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Mark Von Zastrow

    Psychiatry and Cellular & Molecular Pharmacology, UCSF, San Francisco, United States
    For correspondence
    mark@vzlab.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1375-6926

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.

Reviewing Editor

  1. Adam Linstedt, Carnegie Mellon University, United States

Version history

  1. Received: April 20, 2020
  2. Accepted: June 8, 2020
  3. Accepted Manuscript published: June 9, 2020 (version 1)
  4. Version of Record published: July 2, 2020 (version 2)

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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  1. André M Lazar
  2. Roshanak Irannejad
  3. Tanya A Baldwin
  4. Aparna B Sundaram
  5. J Silvio Gutkind
  6. Asuka Inoue
  7. Carmen W Dessauer
  8. Mark Von Zastrow
(2020)
G protein-regulated endocytic trafficking of adenylyl cyclase type 9
eLife 9:e58039.
https://doi.org/10.7554/eLife.58039

Share this article

https://doi.org/10.7554/eLife.58039

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