Crk proteins transduce FGF signaling to promote lens fiber cell elongation

  1. Tamica N Collins
  2. Yingyu Mao
  3. Hongge Li
  4. Michael Bouaziz
  5. Angela Hong
  6. Gen-Sheng Feng
  7. Fen Wang
  8. Lawrence A Quilliam
  9. Lin Chen
  10. Taeju Park
  11. Tom Curran
  12. Xin Zhang  Is a corresponding author
  1. Columbia University, United States
  2. University of California, San Diego, United States
  3. Texas A&M, United States
  4. Indiana University School of Medicine, United States
  5. Third Military Medical University, China
  6. Children's Mercy Kansas City, United States

Abstract

Specific cell shapes are fundamental to the organization and function of multicellular organisms. Fibroblast Growth Factor (FGF) signaling induces the elongation of lens fiber cells during vertebrate lens development. Nonetheless, exactly how this extracellular FGF signal is transmitted to the cytoskeletal network has previously not been determined. Here, we show that the Crk family of adaptor proteins, Crk and Crkl, are required for mouse lens morphogenesis but not differentiation. Genetic ablation and epistasis experiments demonstrated that Crk and Crkl play overlapping roles downstream of FGF signaling in order to regulate lens fiber cell elongation. Upon FGF stimulation, Crk proteins were found to interact with Frs2, Shp2 and Grb. The loss of Crk proteins was partially compensated for by the activation of Ras and Rac signaling. These results reveal that Crk proteins are important partners of the Frs2/Shp2/Grb2 complex in mediating FGF signaling, specifically promoting cell shape changes.

Article and author information

Author details

  1. Tamica N Collins

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yingyu Mao

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hongge Li

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Bouaziz

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Angela Hong

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Gen-Sheng Feng

    Department of Pathology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Fen Wang

    Center for Cancer Biology and Nutrition, Texas A&M, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Lawrence A Quilliam

    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Lin Chen

    Department of Rehabilitation Medicine, Third Military Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Taeju Park

    The Children's Research Institute, Children's Mercy Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Tom Curran

    The Children's Research Institute, Children's Mercy Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Xin Zhang

    Department of Ophthalmology, Columbia University, New York, United States
    For correspondence
    xz2369@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5555-0825

Funding

National Eye Institute (EY017061)

  • Tamica N Collins
  • Yingyu Mao
  • Hongge Li
  • Angela Hong
  • Xin Zhang

National Eye Institute (5P30EY019007)

  • Xin Zhang

Research to Prevent Blindness (Jules and Doris Stein professorship)

  • Xin Zhang

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

Reviewing Editor

  1. Valerie Horsley, Yale University, United States

Ethics

Animal experimentation: Mouse maintenance and experimentation was performed according to protocols approved by Columbia University Institutional Animal Care and Use Committee (protocol AAAR0429).

Version history

  1. Received: October 7, 2017
  2. Accepted: January 23, 2018
  3. Accepted Manuscript published: January 23, 2018 (version 1)
  4. Version of Record published: February 19, 2018 (version 2)

Copyright

© 2018, Collins 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. Tamica N Collins
  2. Yingyu Mao
  3. Hongge Li
  4. Michael Bouaziz
  5. Angela Hong
  6. Gen-Sheng Feng
  7. Fen Wang
  8. Lawrence A Quilliam
  9. Lin Chen
  10. Taeju Park
  11. Tom Curran
  12. Xin Zhang
(2018)
Crk proteins transduce FGF signaling to promote lens fiber cell elongation
eLife 7:e32586.
https://doi.org/10.7554/eLife.32586

Share this article

https://doi.org/10.7554/eLife.32586

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