ArticleMolecular biology of the cell2012
PLCζ causes Ca(2+) oscillations in mouse eggs by targeting intracellular and not plasma membrane PI(4,5)P(2).
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Assessing the impact of calcium ionophore on pregnancy outcomes in artificial oocyte activation cycles: a 10-year update of systematic review and meta-analysis.Journal of assisted reproduction and genetics · 2025Pooled it
- Clinical Features and PLCZ1 Gene Variants in Two Cases of Male Infertility: A Case Series and Literature Review.Molecular genetics & genomic medicine · 2026Review
- PIP5K1A-PIP2-RhoA Signaling Orchestrates Membrane Remodeling during Early Porcine Embryo Development.International journal of biological sciences · 2026Article
- A Novel PLCζ Mutation Linked to Male Factor Infertility Induces a Gain-of-Function Effect on CaInternational journal of molecular sciences · 2025Article
- Phospholipase Cζ, the Molecular Spark of Fertilization and Male Infertility: Insights from Bench to Bedside.Medicina (Kaunas, Lithuania) · 2025Review
- Structural Implications of H233L and H398P Mutations in Phospholipase Cζ: A Full-Atom Molecular Dynamics Study on Infertility-Associated Dysfunctions.International journal of molecular sciences · 2025Article
- The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice.Human reproduction (Oxford, England) · 2024Article
- Development of Recombinant PLC-Zeta Protein as a Therapeutic Intervention for the Clinical Treatment of Oocyte Activation Failure.Biomedicines · 2024Article
- Molecular Mechanism of Oocyte Activation in Mammals: Past, Present, and Future Directions.Biomolecules · 2024Review
- The signal that stimulates mammalian embryo development.Frontiers in cell and developmental biology · 2024Review
- Calcium signaling in oocyte quality and functionality and its application.Frontiers in endocrinology · 2024Review
- Phospholipase C Zeta 1 (PLCZ1): The Function and Potential for Fertility Assessment and In Vitro Embryo Production in Cattle and Horses.Veterinary sciences · 2023Review
- Sperm-Induced CaCells · 2023Review
- Activation Mechanisms and Diverse Functions of Mammalian Phospholipase C.Biomolecules · 2023Review
- The Therapeutic and Diagnostic Potential of Phospholipase C Zeta, Oocyte Activation, and Calcium in Treating Human Infertility.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Artificial oocyte activation with CaFrontiers in endocrinology · 2023Article
- Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application.Human reproduction open · 2022Review
- The carboxy terminal coiled-coil modulates Orai1 internalization during meiosis.Scientific reports · 2021Article
- Diagnosis and Treatment of Male Infertility-Related Fertilization Failure.Journal of clinical medicine · 2020Review
- Modulators of calcium signalling at fertilization.Open biology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Sperm-specific phospholipase C ζ (PLCζ) activates embryo development by triggering intracellular Ca(2+) oscillations in mammalian eggs indistinguishable from those at fertilization. Somatic PLC isozymes generate inositol 1,4,5-trisphophate-mediated Ca(2+) release by hydrolyzing phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in the plasma membrane. Here we examine the subcellular source of PI(4,5)P(2) targeted by sperm PLCζ in mouse eggs. By monitoring egg plasma membrane PI(4,5)P(2) with a green fluorescent protein-tagged PH domain, we show that PLCζ effects minimal loss of PI(4,5)P(2) from the oolemma in contrast to control PLCδ1, despite the much higher potency of PLCζ in eliciting Ca(2+) oscillations. Specific depletion of this PI(4,5)P(2) pool by plasma membrane targeting of an inositol polyphosphate-5-phosphatase (Inp54p) blocked PLCδ1-mediated Ca(2+) oscillations but not those stimulated by PLCζ or sperm. Immunolocalization of PI(4,5)P(2), PLCζ, and catalytically inactive PLCζ (ciPLCζ) revealed their colocalization to distinct vesicular structures inside the egg cortex. These vesicles displayed decreased PI(4,5)P(2) after PLCζ injection. Targeted depletion of vesicular PI(4,5)P(2) by expression of ciPLCζ-fused Inp54p inhibited the Ca(2+) oscillations triggered by PLCζ or sperm but failed to affect those mediated by PLCδ1. In contrast to somatic PLCs, our data indicate that sperm PLCζ induces Ca(2+) mobilization by hydrolyzing internal PI(4,5)P(2) stores, suggesting that the mechanism of mammalian fertilization comprises a novel phosphoinositide signaling pathway.
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Registered trials
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.