1. Cell Biology

Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate Retriever-mediated recycling on endosomes

  1. Sai Srinivas Panapakkam Giridharan
  2. Guangming Luo
  3. Pilar Rivero-Rios
  4. Noah Steinfeld
  5. Helene Tronchere
  6. Amika Singla
  7. Ezra Burstein
  8. Daniel D Billadeau
  9. Michael A Sutton
  10. Lois S Weisman  Is a corresponding author
  1. University of Michigan-Ann Arbor, United States
  2. INSERM U1048 I2MC, France
  3. The University of Texas Southwestern Medical Center, United States
  4. Mayo Clinic, United States
https://doi.org/10.7554/eLife.69709
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Cite this article
  1. Sai Srinivas Panapakkam Giridharan
  2. Guangming Luo
  3. Pilar Rivero-Rios
  4. Noah Steinfeld
  5. Helene Tronchere
  6. Amika Singla
  7. Ezra Burstein
  8. Daniel D Billadeau
  9. Michael A Sutton
  10. Lois S Weisman
(2022)
Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate Retriever-mediated recycling on endosomes
eLife 11:e69709.
https://doi.org/10.7554/eLife.69709
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Abstract

Cell-surface receptors control how cells respond to their environment. Many cell-surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH and CCC complexes. Here, using mammalian cells, we discover that PIKfyve and its upstream PI3-kinase VPS34 positively regulate this pathway. VPS34 produces PI3P, which is the substrate for PIKfyve to generate PI3,5P2. We show that PIKfyve controls recycling of cargoes including integrins, receptors that control cell migration. Furthermore, endogenous PIKfyve colocalizes with SNX17, Retriever, WASH and CCC complexes on endosomes. Importantly, PIKfyve inhibition results displacement of Retriever and CCC from endosomes. In addition, we show that recruitment of SNX17 is an early step and requires VPS34. These discoveries suggest that VPS34 and PIKfyve coordinate an ordered pathway to regulate recycling from endosomes and suggest how PIKfyve functions in cell migration.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sai Srinivas Panapakkam Giridharan

    Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Guangming Luo

    Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Pilar Rivero-Rios

    Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Noah Steinfeld

    Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Helene Tronchere

    INSERM U1048 I2MC, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.

  6. Amika Singla

    Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Ezra Burstein

    Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4341-6367

  8. Daniel D Billadeau

    Division of Oncology Research, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Michael A Sutton

    Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1593-727X

  10. Lois S Weisman

    Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    For correspondence
    lweisman@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7740-9785

Funding

National Institute of Neurological Disorders and Stroke (Research Project Grant R01 NS064015)

  • Lois S Weisman

National Institute of Neurological Disorders and Stroke (Research Project Grant R01-NS099340)

  • Lois S Weisman

National Institute of Diabetes and Digestive and Kidney Diseases (Research Project Grant R01-DK107733)

  • Ezra Burstein
  • Daniel D Billadeau

American Heart Association (Postdoctoral Fellowship 14POST20480137)

  • Sai Srinivas Panapakkam Giridharan

American Heart Association (Postdoctoral Fellowship 19POST34450253)

  • Guangming Luo

University of Michigan Protein Folding Diseases Fast Forward Initiative (Pilot grant)

  • Lois S Weisman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#A3114-01) of the University of Michigan. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Michigan (Approval # PRO00010100).

Copyright

© 2022, Giridharan 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. Sai Srinivas Panapakkam Giridharan
  2. Guangming Luo
  3. Pilar Rivero-Rios
  4. Noah Steinfeld
  5. Helene Tronchere
  6. Amika Singla
  7. Ezra Burstein
  8. Daniel D Billadeau
  9. Michael A Sutton
  10. Lois S Weisman
(2022)
Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate Retriever-mediated recycling on endosomes
eLife 11:e69709.
https://doi.org/10.7554/eLife.69709

Share this article

https://doi.org/10.7554/eLife.69709

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