ArticleThe Journal of biological chemistry2010
Calcineurin-mediated dephosphorylation of synaptotagmin VI is necessary for acrosomal exocytosis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Membrane Fusions During Mammalian Fertilization.Advances in experimental medicine and biology · 2026Review
- 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
- PP1, PP2A and PP2B Interplay in the Regulation of Sperm Motility: Lessons from Protein Phosphatase Inhibitors.International journal of molecular sciences · 2022Review
- Calcineurin Aα Contributes to IgE-Dependent Mast-Cell Mediator Secretion in Allergic Inflammation.Journal of innate immunity · 2022Article
- 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
- Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals.Frontiers in cell and developmental biology · 2019Review
- Epididymal approaches to male contraception.Basic and clinical andrology · 2018Review
- Molecular changes and signaling events occurring in spermatozoa during epididymal maturation.Andrology · 2017Review
- Redistribution of soluble N-ethylmaleimide-sensitive-factor attachment protein receptors in mouse sperm membranes prior to the acrosome reaction.Biology of reproduction · 2017Article
- Dynamin 2 is essential for mammalian spermatogenesis.Scientific reports · 2016Article
- T-type Ca2+ channels in spermatogenic cells and sperm.Pflugers Archiv : European journal of physiology · 2014Review
- Cytosolic Ca(2+) as a multifunctional modulator is required for spermiogenesis in Ascaris suum.Protein & cell · 2013Article
- Isolation of a calcium-binding protein of the acrosomal membrane of bovine spermatozoa.The international journal of biochemistry & cell biology · 2013Article
- K+ and Cl- channels and transporters in sperm function.Current topics in developmental biology · 2013Review
- Protein phosphatases decrease their activity during capacitation: a new requirement for this event.PloS one · 2013Article
- MARCKS protein is phosphorylated and regulates calcium mobilization during human acrosomal exocytosis.PloS one · 2013Article
- Mouse sperm membrane potential hyperpolarization is necessary and sufficient to prepare sperm for the acrosome reaction.The Journal of biological chemistry · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated secretion is a fundamental process underlying the function of many cell types. In particular, acrosomal exocytosis in mammalian sperm is essential for egg fertilization. In general, exocytosis is initiated by a cytosolic calcium increase. In this report we show that calcium affects several factors during human sperm acrosomal exocytosis. By using an antibody that specifically recognizes synaptotagmin VI phosphorylated at the polybasic region of the C2B domain, we showed that a calcium-dependent dephosphorylation of this protein occurred at early stages of the acrosomal exocytosis in streptolysin O-permeabilized sperm. We identified the phosphatase as calcineurin and showed that the activity of this enzyme is absolutely required during the early steps of the secretory process. When added to sperm, an inhibitor-insensitive, catalytically active domain of calcineurin was able to rescue the effect of the specific calcineurin inhibitor cyclosporin A. This same domain dephosphorylated recombinant synaptotagmin VI C2B domain, validating this protein as a new substrate for calcineurin. When sperm were treated with catalytically active calcineurin before stimulation, exocytosis was inhibited, an effect that was rescued by the phosphomimetic synaptotagmin VI C2B-T418E,T419E mutant domain. These observations indicate that synaptotagmin must be dephosphorylated at a specific window of time and suggest that phosphorylated synaptotagmin has an active role at early stages of the acrosomal exocytosis.
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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.