ArticleBiology of reproduction2018
Isoform-specific requirement for GSK3α in sperm for male fertility.
Article in Biology of reproduction, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
The trial behind it
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Physiological basis of contraceptive function of a GSK3α-selective inhibitor, manifested during epididymal sperm maturation.Molecular human reproduction · 2026Article
- PP1γ1 is unable to substitute for the mammal-specific PP1γ2 isoform to support male fertility and sperm function.Reproduction (Cambridge, England) · 2025Article
- GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model.International journal of molecular sciences · 2024Review
- GSK3: A potential target and pending issues for treatment of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Review
- Differential role of bovine serum albumin and HCO3- in the regulation of GSK3 alpha during mouse sperm capacitation.Molecular human reproduction · 2024Article
- Review
- Interactomes of Glycogen Synthase Kinase-3 Isoforms.Journal of proteome research · 2023Article
- Glycogen Synthase Kinase-3 Isoform Variants and Their Inhibitory Phosphorylation in Human Testes and Spermatozoa.The world journal of men's health · 2023Article
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- The exploration of miRNAs and mRNA profiles revealed the molecular mechanisms of cattle-yak male infertility.Frontiers in veterinary science · 2022Article
- Opposing Roles of GSK3α and GSK3β Phosphorylation in Platelet Function and Thrombosis.International journal of molecular sciences · 2021Article
- Review
- Polyamines Influence Mouse Sperm Channels Activity.International journal of molecular sciences · 2021Article
- Characterizing the Role of Glycogen Synthase Kinase-3α/β in Macrophage Polarization and the Regulation of Pro-Atherogenic Pathways in Cultured LdlrFrontiers in immunology · 2021Article
- Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis.Brain sciences · 2020Review
- Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Plasmodium berghei serine/threonine protein phosphatase PP5 plays a critical role in male gamete fertility.International journal for parasitology · 2019Article
- Isoform-specific GSK3A activity is negatively correlated with human sperm motility.Molecular human reproduction · 2019Article
- The protein phosphatase isoform PP1γ1 substitutes for PP1γ2 to support spermatogenesis but not normal sperm function and fertility†.Biology of reproduction · 2019Article
- Regulators of the protein phosphatase PP1γ2, PPP1R2, PPP1R7, and PPP1R11 are involved in epididymal sperm maturation.Journal of cellular physiology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Glycogen synthase kinase 3 (GSK3) is a highly conserved protein kinase regulating key cellular functions. Its two isoforms, GSK3α and GSK3β, are encoded by distinct genes. In most tissues the two isoforms are functionally interchangeable, except in the developing embryo where GSK3β is essential. One functional allele of either of the two isoforms is sufficient to maintain normal tissue functions. Both GSK3 isoforms, present in sperm from several species including human, are suggested to play a role in epididymal initiation of sperm motility. Using genetic approaches, we have tested requirement for each of the two GSK3 isoforms in testis and sperm. Both GSK3 isoforms are expressed at high levels during the onset of spermatogenesis. Conditional knockout of GSK3α, but not GSK3β, in developing testicular germ cells in mice results in male infertility. Mice lacking one allele each of GSK3α and GSK3β are fertile. Despite overlapping expression and localization in differentiating spermatids, GSK3β does not substitute for GSK3α. Loss of GSK3α impairs sperm hexokinase activity resulting in low ATP levels. Net adenine nucleotide levels in caudal sperm lacking GSK3α resemble immature caput epididymal sperm. Changes in the association of the protein phosphatase PP1γ2 with its protein interactors occurring during epididymal sperm maturation is impaired in sperm lacking GSK3α. The isoform-specific requirement for GSK3α is likely due to its specific binding partners in the sperm principal piece. Testis and sperm are unique in their specific requirement of GSK3α for normal function and male fertility.
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Registered trials
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