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The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca2+ signaling

  1. Bo Gong
  2. Weimin Shen
  3. Wanghua Xiao
  4. Yaping Meng
  5. Anming Meng  Is a corresponding author
  6. Shunji Jia  Is a corresponding author
  1. Tsinghua University, China
Research Article
  • Cited 8
  • Views 1,139
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Cite this article as: eLife 2017;6:e26362 doi: 10.7554/eLife.26362

Abstract

The non-canonical Wnt/Ca2+ signaling pathway plays important roles in embryonic development, tissue formation and diseases. However, it is unclear how the Wnt ligand-stimulated, G protein-coupled receptor Frizzled activates phospholipases for calcium release. Here, we report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). Depletion of sec14l3 attenuates Wnt/Ca2+ responsive activity and causes convergent and extension (CE) defects in zebrafish embryos. Biochemical analyses in mammalian cells indicate that Sec14l3-GDP forms complex with Frizzled and Dishevelled; Wnt ligand binding of Frizzled induces translocation of Sec14l3 to the plasma membrane; and then Sec14l3-GTP binds to and activates phospholipase Cδ4a (Plcδ4a); subsequently, Plcδ4a initiates phosphatidylinositol-4,5-bisphosphate (PIP2) signaling, ultimately stimulating calcium release. Furthermore, Plcδ4a can act as a GTPase-activating protein to accelerate the hydrolysis of Sec14l3-bound GTP to GDP. Our data provide a new insight into GTPase protein-coupled Wnt/Ca2+ signaling transduction.<sub/>

Article and author information

Author details

  1. Bo Gong

    State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Weimin Shen

    State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Wanghua Xiao

    State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yaping Meng

    State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Anming Meng

    State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    mengam@mail.tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  6. Shunji Jia

    State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    jiasj@mail.tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8678-1714

Funding

National Natural Science Foundation of China (31522035)

  • Shunji Jia

National Natural Science Foundation of China (31371460)

  • Shunji Jia

Ministry of Science and Technology of the People's Republic of China (2012CB945100)

  • Shunji Jia

Ministry of Science and Technology of the People's Republic of China (2011CB943800)

  • Anming Meng

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

Ethics

Animal experimentation: Fishes were handled according to the institutional animal care and use committee (IACUC) protocols (AP#13-MAM1), which were approved and permitted by the Tsinghua University Animal Care and Use Committee.

Reviewing Editor

  1. Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China

Publication history

  1. Received: February 27, 2017
  2. Accepted: April 30, 2017
  3. Accepted Manuscript published: May 2, 2017 (version 1)
  4. Version of Record published: May 9, 2017 (version 2)

Copyright

© 2017, Gong 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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