Caenorhabditis elegans PIEZO channel coordinates multiple reproductive tissues to govern ovulation

  1. Xiaofei Bai
  2. Jeff W Bouffard
  3. Avery Lord
  4. Katherine Brugman
  5. Paul W Sternberg
  6. Erin J Cram
  7. Andy Golden  Is a corresponding author
  1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States
  2. Northeastern University, United States
  3. California Institute of Technology, United States
  4. Howard Hughes Medical Institute, California Institute of Technology, United States

Abstract

PIEZO1 and PIEZO2 are newly identified mechano-sensitive ion channels that exhibit a preference for calcium in response to mechanical stimuli. In this study, we discovered the vital roles of pezo-1, the sole PIEZO ortholog in C. elegans, in regulating reproduction. A number of deletion alleles as well as a putative gain-of-function mutant of PEZO-1 caused a severe reduction in brood size. In vivo observations showed that oocytes undergo a variety of transit defects as they enter and exit the spermatheca during ovulation. Post ovulation oocytes were frequently damaged during spermathecal contraction. However, the calcium signaling was not dramatically changed in the pezo-1 mutants during ovulation. Loss of PEZO-1 also revealed an inability of self-sperm to properly navigate back to the spermatheca after being pushed out of the spermatheca during ovulation. These findings suggest that PEZO-1 acts in different reproductive tissues to promote proper ovulation and fertilization in C. elegans.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures and Supplemental Figures

Article and author information

Author details

  1. Xiaofei Bai

    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jeff W Bouffard

    Department of Bioengineering, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Avery Lord

    Department of Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Katherine Brugman

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul W Sternberg

    Division of Biology & BIological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7699-0173
  6. Erin J Cram

    Department of Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Andy Golden

    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    For correspondence
    andyg@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8599-2031

Funding

National Institute of General Medical Sciences (GM110268)

  • Erin J Cram

NIH Clinical Center (R01 NS113119)

  • Paul W Sternberg

NIH Clinical Center (R24 0D023041)

  • Paul W Sternberg

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

Reviewing Editor

  1. Diana S Chu, San Francisco State University, United States

Publication history

  1. Received: November 14, 2019
  2. Accepted: June 2, 2020
  3. Accepted Manuscript published: June 3, 2020 (version 1)
  4. Accepted Manuscript updated: June 4, 2020 (version 2)
  5. Version of Record published: July 7, 2020 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,783
    Page views
  • 452
    Downloads
  • 10
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Xiaofei Bai
  2. Jeff W Bouffard
  3. Avery Lord
  4. Katherine Brugman
  5. Paul W Sternberg
  6. Erin J Cram
  7. Andy Golden
(2020)
Caenorhabditis elegans PIEZO channel coordinates multiple reproductive tissues to govern ovulation
eLife 9:e53603.
https://doi.org/10.7554/eLife.53603

Further reading

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Tsuyoshi Imasaki et al.
    Research Article

    Microtubules are dynamic polymers consisting of αβ-tubulin heterodimers. The initial polymerization process, called microtubule nucleation, occurs spontaneously via αβ-tubulin. Since a large energy barrier prevents microtubule nucleation in cells, the γ-tubulin ring complex is recruited to the centrosome to overcome the nucleation barrier. However, a considerable number of microtubules can polymerize independently of the centrosome in various cell types. Here, we present evidence that the minus-end-binding calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) serves as a strong nucleator for microtubule formation by significantly reducing the nucleation barrier. CAMSAP2 co-condensates with αβ-tubulin via a phase separation process, producing plenty of nucleation intermediates. Microtubules then radiate from the co-condensates, resulting in aster-like structure formation. CAMSAP2 localizes at the co-condensates and decorates the radiating microtubule lattices to some extent. Taken together, these in vitro findings suggest that CAMSAP2 supports microtubule nucleation and growth by organizing a nucleation centre as well as by stabilizing microtubule intermediates and growing microtubules.

    1. Cell Biology
    2. Developmental Biology
    Katelyn J Hoff et al.
    Research Article Updated

    Heterozygous, missense mutations in α- or β-tubulin genes are associated with a wide range of human brain malformations, known as tubulinopathies. We seek to understand whether a mutation’s impact at the molecular and cellular levels scale with the severity of brain malformation. Here, we focus on two mutations at the valine 409 residue of TUBA1A, V409I, and V409A, identified in patients with pachygyria or lissencephaly, respectively. We find that ectopic expression of TUBA1A-V409I/A mutants disrupt neuronal migration in mice and promote excessive neurite branching and a decrease in the number of neurite retraction events in primary rat neuronal cultures. These neuronal phenotypes are accompanied by increased microtubule acetylation and polymerization rates. To determine the molecular mechanisms, we modeled the V409I/A mutants in budding yeast and found that they promote intrinsically faster microtubule polymerization rates in cells and in reconstitution experiments with purified tubulin. In addition, V409I/A mutants decrease the recruitment of XMAP215/Stu2 to plus ends in budding yeast and ablate tubulin binding to TOG (tumor overexpressed gene) domains. In each assay tested, the TUBA1A-V409I mutant exhibits an intermediate phenotype between wild type and the more severe TUBA1A-V409A, reflecting the severity observed in brain malformations. Together, our data support a model in which the V409I/A mutations disrupt microtubule regulation typically conferred by XMAP215 proteins during neuronal morphogenesis and migration, and this impact on tubulin activity at the molecular level scales with the impact at the cellular and tissue levels.