ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Physiological basis of contraceptive function of a GSK3α-selective inhibitor, manifested during epididymal sperm maturation.Molecular human reproduction · 2026Article
- FK506 binding protein 12.6-mediated inhibition of sperm-specific calcineurin is essential for FK506-induced male infertility by disturbing the homeostasis of calcium and mitochondria.Molecular biomedicine · 2025Article
- PP1γ1 is unable to substitute for the mammal-specific PP1γ2 isoform to support male fertility and sperm function.Reproduction (Cambridge, England) · 2025Article
- Differential role of bovine serum albumin and HCO3- in the regulation of GSK3 alpha during mouse sperm capacitation.Molecular human reproduction · 2024Article
- PP1, PP2A and PP2B Interplay in the Regulation of Sperm Motility: Lessons from Protein Phosphatase Inhibitors.International journal of molecular sciences · 2022Review
- Investigation of Copy Number Variations (CNVs) of the GoatAnimals : an open access journal from MDPI · 2022Article
- SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A multiplier peroxiporin signal transduction pathway powers piscine spermatozoa.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals.Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Glycogen synthase kinase 3 (GSK3) was identified as an enzyme regulating sperm protein phosphatase. The GSK3α paralog, but not GSK3β, is essential for sperm function. Sperm lacking GSK3α display altered motility and are unable to undergo hyperactivation, which is essential for fertilization. Male mice lacking sperm-specific calcineurin (PP2B), a calcium regulated phosphatase, in testis and sperm, are also infertile. Loss of PP2B results in impaired epididymal sperm maturation and motility. The phenotypes of GSK3α and PP2B knockout mice are similar, prompting us to examine the interrelationship between these two enzymes in sperm. High calcium levels must exist to permit catalytically active calcineurin to function during epididymal sperm maturation. Total and free calcium levels are high in immotile compared to motile epididymal sperm. Inhibition of calcineurin by FK506 results in an increase in the net phosphorylation and a consequent decrease in catalytic activity of sperm GSK3. The inhibitor FK506 and an isoform-selective inhibitor of GSK3α, BRD0705, also inhibited fertilization of eggs in vitro. Interrelated functions of GSK3α and sperm PP2B are essential during epididymal sperm maturation and during fertilization. Our results should enable the development of male contraceptives targeting one or both enzymes.
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