1. Biochemistry and Chemical Biology
  2. Cell Biology

Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF

  1. Guo Cheng
  2. Ming Zhong
  3. Riki Kawaguchi
  4. Miki Kassai
  5. Muayyad Al-Ubaidi
  6. Jun Deng
  7. Mariam Ter-Stepanian
  8. Hui Sun  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, Los Angeles, United States
  2. University of Oklahoma Health Sciences Center, United States
https://doi.org/10.7554/eLife.05401
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Cite this article
  1. Guo Cheng
  2. Ming Zhong
  3. Riki Kawaguchi
  4. Miki Kassai
  5. Muayyad Al-Ubaidi
  6. Jun Deng
  7. Mariam Ter-Stepanian
  8. Hui Sun
(2014)
Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF
eLife 3:e05401.
https://doi.org/10.7554/eLife.05401
  2. Download BibTeX
  3. Download .RIS

Abstract

Pigment Epithelium Derived Factor (PEDF) is a secreted factor that has broad biological activities. It was first identified as a neurotrophic factor and later as the most potent natural antiangiogenic factor, a stem cell niche factor, and an inhibitor of cancer cell growth. Numerous animal models demonstrated its therapeutic value in treating blinding diseases and diverse cancer types. A long-standing challenge is to reveal how PEDF acts on its target cells and the identities of the cell-surface receptors responsible for its activities. Here we report the identification of transmembrane proteins PLXDC1 and PLXDC2 as cell-surface receptors for PEDF. Using distinct cellular models, we demonstrate their cell type-specific receptor activities through loss of function and gain of function studies. Our experiments suggest that PEDF receptors form homooligomers under basal conditions, and PEDF dissociates the homooligomer to activate the receptors. Mutations in the intracellular domain can have profound effects on receptor activities.

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Author details

  1. Guo Cheng

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Ming Zhong

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Riki Kawaguchi

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Miki Kassai

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Muayyad Al-Ubaidi

    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Jun Deng

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Mariam Ter-Stepanian

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Hui Sun

    Department of Physiology, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    hsun@mednet.ucla.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2014, Cheng 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. Guo Cheng
  2. Ming Zhong
  3. Riki Kawaguchi
  4. Miki Kassai
  5. Muayyad Al-Ubaidi
  6. Jun Deng
  7. Mariam Ter-Stepanian
  8. Hui Sun
(2014)
Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF
eLife 3:e05401.
https://doi.org/10.7554/eLife.05401

Share this article

https://doi.org/10.7554/eLife.05401

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