Novel LOTUS-domain proteins are organizational hubs that recruit C. elegans Vasa to germ granules
- New York University, United States
- McGill University, Canada
- Max Delbrück Center for Molecular Medicine, Germany
- New York University Abu Dhabi, United Arab Emirates
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.
Article and author information
Author details
Kristin C Gunsalus
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.
Reviewing Editor
- Michael Buszczak, University of Texas Southwestern Medical Center, United States
Version history
- Received: July 8, 2020
- Accepted: June 27, 2021
- Accepted Manuscript published: July 5, 2021 (version 1)
- Version of Record published: August 3, 2021 (version 2)
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.
Metrics
-
- 2,579
- views
-
- 234
- 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)
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
Further reading
-
- Cell Biology
Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.
-
- Cell Biology
- Stem Cells and Regenerative Medicine
Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from Cd47−/− mice. Expression of several genes associated with early stages of erythropoiesis was elevated in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors were more abundant in Cd47−/− spleens but significantly depleted in Thbs1−/− spleens. Single-cell transcriptome and flow cytometry analyses indicated that loss of CD47 is associated with accumulation and increased proliferation in spleen of Ter119−CD34+ progenitors and Ter119+CD34− committed erythroid progenitors with elevated mRNA expression of Kit, Ermap, and Tfrc. Induction of committed erythroid precursors is consistent with the known function of CD47 to limit the phagocytic removal of aged erythrocytes. Conversely, loss of thrombospondin-1 delays the turnover of aged red blood cells, which may account for the suppression of committed erythroid precursors in Thbs1−/− spleens relative to basal levels in wild-type mice. In addition to defining a role for CD47 to limit extramedullary erythropoiesis, these studies reveal a thrombospondin-1-dependent basal level of extramedullary erythropoiesis in adult mouse spleen.
