Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling

  1. Shelly TH McClatchey
  2. Zheng Wang
  3. Lara M Linden
  4. Eric L Hastie
  5. Lin Wang
  6. Wanqing Shen
  7. Alan Chen
  8. Qiuyi Chi
  9. David R Sherwood  Is a corresponding author
  1. Duke University, United States
  2. Huazhong University of Science and Technology, China

Abstract

Epithelial cells and their underlying basement membranes (BMs) slide along each other to renew epithelia, shape organs, and enlarge BM openings. How BM sliding is controlled, however, is poorly understood. Using genetic and live cell imaging approaches during uterine-vulval attachment in C. elegans, we have discovered that the invasive uterine anchor cell activates Notch signaling in neighboring uterine cells at the boundary of the BM gap through which it invades to promote BM sliding. Through an RNAi screen, we found that Notch activation upregulates expression of ctg-1, which encodes a Sec14-GOLD protein and member of the Sec14 phosphatidylinositol-transfer protein superfamily that is implicated in vesicle trafficking. Through photobleaching, targeted knockdown, and cell-specific rescue, our results suggest that CTG-1 restricts BM adhesion receptor DGN-1 (dystroglycan) trafficking to the cell-BM interface, which promotes BM sliding. Together, these studies reveal a new morphogenetic signaling pathway that controls BM sliding to remodel tissues.

Article and author information

Author details

  1. Shelly TH McClatchey

    Department of Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zheng Wang

    Center for Tissue Engineering and Regenerative Medicine, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Lara M Linden

    Department of Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eric L Hastie

    Department of Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lin Wang

    Center for Tissue Engineering and Regenerative Medicine, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Wanqing Shen

    Center for Tissue Engineering and Regenerative Medicine, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Alan Chen

    Department of Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Qiuyi Chi

    Department of Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. David R Sherwood

    Department of Biology, Duke University, Durham, United States
    For correspondence
    david.sherwood@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2245-2334

Funding

National Institute of General Medical Sciences (GM079320)

  • David R Sherwood

National Institute of General Medical Sciences (GM100083)

  • David R Sherwood

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

Reviewing Editor

  1. Janet Rossant, University of Toronto, Canada

Version history

  1. Received: April 25, 2016
  2. Accepted: September 22, 2016
  3. Accepted Manuscript published: September 23, 2016 (version 1)
  4. Version of Record published: October 12, 2016 (version 2)

Copyright

© 2016, McClatchey 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.

Metrics

  • 1,232
    views
  • 312
    downloads
  • 12
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shelly TH McClatchey
  2. Zheng Wang
  3. Lara M Linden
  4. Eric L Hastie
  5. Lin Wang
  6. Wanqing Shen
  7. Alan Chen
  8. Qiuyi Chi
  9. David R Sherwood
(2016)
Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling
eLife 5:e17218.
https://doi.org/10.7554/eLife.17218

Share this article

https://doi.org/10.7554/eLife.17218

Further reading

    1. Cell Biology
    Jun Yang, Shitian Zou ... Xiaochun Bai
    Research Article

    Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. A genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly disruption of two nuclear receptors, Rara or Nr1h3, accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.

    1. Cancer Biology
    2. Cell Biology
    Stefanie Schmieder
    Insight

    Mutations in the gene for β-catenin cause liver cancer cells to release fewer exosomes, which reduces the number of immune cells infiltrating the tumor.