IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-12221-6.html
   My bibliography  Save this article

Endosomal PI(3)P regulation by the COMMD/CCDC22/CCDC93 (CCC) complex controls membrane protein recycling

Author

Listed:
  • Amika Singla

    (University of Texas Southwestern Medical Center)

  • Alina Fedoseienko

    (College of Medicine, Mayo Clinic)

  • Sai S. P. Giridharan

    (University of Michigan)

  • Brittany L. Overlee

    (College of Medicine, Mayo Clinic)

  • Adam Lopez

    (University of Texas Southwestern Medical Center)

  • Da Jia

    (Sichuan University)

  • Jie Song

    (University of Texas Southwestern Medical Center)

  • Kayci Huff-Hardy

    (University of Texas Southwestern Medical Center)

  • Lois Weisman

    (University of Michigan)

  • Ezra Burstein

    (University of Texas Southwestern Medical Center)

  • Daniel D. Billadeau

    (College of Medicine, Mayo Clinic)

Abstract

Protein recycling through the endolysosomal system relies on molecular assemblies that interact with cargo proteins, membranes, and effector molecules. Among them, the COMMD/CCDC22/CCDC93 (CCC) complex plays a critical role in recycling events. While CCC is closely associated with retriever, a cargo recognition complex, its mechanism of action remains unexplained. Herein we show that CCC and retriever are closely linked through sharing a common subunit (VPS35L), yet the integrity of CCC, but not retriever, is required to maintain normal endosomal levels of phosphatidylinositol-3-phosphate (PI(3)P). CCC complex depletion leads to elevated PI(3)P levels, enhanced recruitment and activation of WASH (an actin nucleation promoting factor), excess endosomal F-actin and trapping of internalized receptors. Mechanistically, we find that CCC regulates the phosphorylation and endosomal recruitment of the PI(3)P phosphatase MTMR2. Taken together, we show that the regulation of PI(3)P levels by the CCC complex is critical to protein recycling in the endosomal compartment.

Suggested Citation

  • Amika Singla & Alina Fedoseienko & Sai S. P. Giridharan & Brittany L. Overlee & Adam Lopez & Da Jia & Jie Song & Kayci Huff-Hardy & Lois Weisman & Ezra Burstein & Daniel D. Billadeau, 2019. "Endosomal PI(3)P regulation by the COMMD/CCDC22/CCDC93 (CCC) complex controls membrane protein recycling," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12221-6
    DOI: 10.1038/s41467-019-12221-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-12221-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-12221-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rebeka Butkovič & Alexander P. Walker & Michael D. Healy & Kerrie E. McNally & Meihan Liu & Tineke Veenendaal & Kohji Kato & Nalan Liv & Judith Klumperman & Brett M. Collins & Peter J. Cullen, 2024. "Mechanism and regulation of cargo entry into the Commander endosomal recycling pathway," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12221-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.