1. Cell Biology
  2. Developmental Biology

Novel LOTUS-domain proteins are organizational hubs that recruit C. elegans Vasa to germ granules

  1. Patricia Giselle Cipriani
  2. Olivia Bay
  3. John Zinno
  4. Michelle Gutwein
  5. Hin Hark Gan
  6. Vinay K Mayya
  7. George Chung
  8. Jia-Xuan Chen
  9. Hala Fahs
  10. Yu Guan
  11. Thomas F Duchaine
  12. Matthias Selbach
  13. Fabio Piano
  14. Kristin C Gunsalus  Is a corresponding author
  1. New York University, United States
  2. McGill University, Canada
  3. Max Delbrück Center for Molecular Medicine, Germany
  4. New York University Abu Dhabi, United Arab Emirates
https://doi.org/10.7554/eLife.60833
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Cite this article
  1. Patricia Giselle Cipriani
  2. Olivia Bay
  3. John Zinno
  4. Michelle Gutwein
  5. Hin Hark Gan
  6. Vinay K Mayya
  7. George Chung
  8. Jia-Xuan Chen
  9. Hala Fahs
  10. Yu Guan
  11. Thomas F Duchaine
  12. Matthias Selbach
  13. Fabio Piano
  14. Kristin C Gunsalus
(2021)
Novel LOTUS-domain proteins are organizational hubs that recruit C. elegans Vasa to germ granules
eLife 10:e60833.
https://doi.org/10.7554/eLife.60833
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Abstract

We describe MIP-1 and MIP-2, novel paralogous C. elegans germ granule components that interact with the intrinsically disordered MEG-3 protein. These proteins promote P granule condensation, form granules independently of MEG-3 in the postembryonic germ line, and balance each other in regulating P granule growth and localization. MIP-1 and MIP-2 each contain two LOTUS domains and intrinsically disordered regions and form homo- and heterodimers. They bind and anchor the Vasa homolog GLH-1 within P granules and are jointly required for coalescence of MEG-3, GLH-1, and PGL proteins. Animals lacking MIP-1 and MIP-2 show temperature-sensitive embryonic lethality, sterility, and mortal germ lines. Germline phenotypes include defects in stem cell self-renewal, meiotic progression, and gamete differentiation. We propose that these proteins serve as scaffolds and organizing centers for ribonucleoprotein networks within P granules that help recruit and balance essential RNA processing machinery to regulate key developmental transitions in the germ line.

Data availability

All mass spectrometry raw data have been deposited to the PRIDE repository with the dataset identifier PXD012852. All other data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2A-C; Figure 2-figure supplement 2; Figure 6A,B; Figure 8E; Figure 9B; Figure 9-figure supplement 1; Figure 10C.

The following data sets were generated

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Author details

  1. Patricia Giselle Cipriani

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Olivia Bay

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. John Zinno

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Michelle Gutwein

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Hin Hark Gan

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Vinay K Mayya

    Goodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  7. George Chung

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Jia-Xuan Chen

    None, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.

  9. Hala Fahs

    Center for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
    Competing interests
    The authors declare that no competing interests exist.

  10. Yu Guan

    Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Thomas F Duchaine

    Goodman Cancer Research Center, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  12. Matthias Selbach

    Department of Protein Dynamics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.

  13. Fabio Piano

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  14. Kristin C Gunsalus

    Center for Genomics and Systems Biology, New York University, New York, United States
    For correspondence
    kcg1@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9769-4624

Funding

New York University Abu Dhabi (ADPHG CGSB)

  • Patricia Giselle Cipriani
  • Hala Fahs
  • Fabio Piano
  • Kristin C Gunsalus

New York University Abu Dhabi

  • Patricia Giselle Cipriani
  • Olivia Bay
  • John Zinno
  • Michelle Gutwein
  • Hin Hark Gan
  • George Chung
  • Fabio Piano
  • Kristin C Gunsalus

Canadian Institutes of Health Research (MOP 123352)

  • Vinay K Mayya
  • Thomas F Duchaine

Charlotte and Leo Karassik Foundation

  • Vinay K Mayya

Bundesministerium für Bildung und Forschung (0315362)

  • Jia-Xuan Chen

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

Copyright

© 2021, Cipriani 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. Patricia Giselle Cipriani
  2. Olivia Bay
  3. John Zinno
  4. Michelle Gutwein
  5. Hin Hark Gan
  6. Vinay K Mayya
  7. George Chung
  8. Jia-Xuan Chen
  9. Hala Fahs
  10. Yu Guan
  11. Thomas F Duchaine
  12. Matthias Selbach
  13. Fabio Piano
  14. Kristin C Gunsalus
(2021)
Novel LOTUS-domain proteins are organizational hubs that recruit C. elegans Vasa to germ granules
eLife 10:e60833.
https://doi.org/10.7554/eLife.60833

Share this article

https://doi.org/10.7554/eLife.60833

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Further reading

    1. Cell Biology

    Proximity labeling identifies LOTUS domain proteins that promote the formation of perinuclear germ granules in C. elegans

    Ian F Price, Hannah L Hertz ... Wen Tang
    Research Article Updated

    The germ line produces gametes that transmit genetic and epigenetic information to the next generation. Maintenance of germ cells and development of gametes require germ granules—well-conserved membraneless and RNA-rich organelles. The composition of germ granules is elusive owing to their dynamic nature and their exclusive expression in the germ line. Using Caenorhabditis elegans germ granule, called P granule, as a model system, we employed a proximity-based labeling method in combination with mass spectrometry to comprehensively define its protein components. This set of experiments identified over 200 proteins, many of which contain intrinsically disordered regions (IDRs). An RNA interference-based screen identified factors that are essential for P granule assembly, notably EGGD-1 and EGGD-2, two putative LOTUS-domain proteins. Loss of eggd-1 and eggd-2 results in separation of P granules from the nuclear envelope, germline atrophy, and reduced fertility. We show that IDRs of EGGD-1 are required to anchor EGGD-1 to the nuclear periphery while its LOTUS domains are required to promote the perinuclear localization of P granules. Taken together, our work expands the repertoire of P granule constituents and provides new insights into the role of LOTUS-domain proteins in germ granule organization.