ArticleProceedings of the National Academy of Sciences of the United States of America2020
A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Molecular mechanisms and translational implications in apoptosis, ferroptosis, pyroptosis, and cuproptosis of spermatogonial stem cells.Cellular and molecular life sciences : CMLS · 2026Review
- Structure of the mouse cytoplasmic lattice.Nature · 2026Article
- NLRP14 modulates the activity of E3 ubiquitin ligases during the oocyte-to-embryo transition.Nature communications · 2026Article
- Genome-Wide Characterization of Sex-Linked Regions in the Sangzhi Horned Toad (Boulenophrys sangzhiensis) Reveals Complex Sex Determination Mechanisms.Molecular ecology resources · 2026Article
- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
- A primordial germ cell-like-cell platform enables CRISPRi screen for epigenetic fertility modifiers.EMBO reports · 2025Article
- RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination.Cell proliferation · 2025Article
- Towards a kingdom of reproductive life - the core sperm proteome.Reproduction (Cambridge, England) · 2025Article
- Evolving Lessons on Metazoan Primordial Germ Cells in Diversity and Development.Molecular reproduction and development · 2025Review
- Male germ cells with Bag5 deficiency show reduced spermiogenesis and exchange of basic nuclear proteins.Cellular and molecular life sciences : CMLS · 2025Article
- From biomolecules to breakthroughs: exosomes as next-generation theranostics in female infertility.Frontiers in cell and developmental biology · 2025Review
- NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.Cellular & molecular biology letters · 2024Article
- Transcriptome analysis of reproductive tract tissues of male river prawn Macrobrachium americanum.Molecular biology reports · 2024Article
- Structural basis of the subcortical maternal complex and its implications in reproductive disorders.Nature structural & molecular biology · 2024Article
- The NLR gene family: from discovery to present day.Nature reviews. Immunology · 2023Review
- Cocktails of NSAIDs and 17α Ethinylestradiol at Environmentally Relevant Doses in Drinking Water Alter Puberty Onset in Mice Intergenerationally.International journal of molecular sciences · 2023Article
- Article
- The role of NOD-like receptors in innate immunity.Frontiers in immunology · 2023Review
- Inactivation ofInternational journal of biological sciences · 2023Article
- Germline stem cells in human.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonad-specific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive failure in both female and male mice. In adult male mice, Nlrp14 knockout (KO) inhibited differentiation of spermatogonial stem cells (SSCs) and meiosis, resulting in trapped SSCs in early stages, severe oligozoospermia, and sperm abnormality. Mechanistically, NLRP14 promoted spermatogenesis by recruiting a chaperone cofactor, BAG2, to bind with HSPA2 and form the NLRP14-HSPA2-BAG2 complex, which strongly inhibited ChIP-mediated HSPA2 polyubiquitination and promoted its nuclear translocation. Finally, loss of HSPA2 protection and BAG2 recruitment by NLRP14 was confirmed in a human nonsense germline variant associated with male sterility. Together, our data highlight a unique proteasome-mediated, noncanonical function of NLRP14 in PGCLC differentiation and spermatogenesis, providing mechanistic insights of gonad-specific NLRs in mammalian germline development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.