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Sperm lacking GSK3\u03b1 display altered motility and are unable to undergo hyperactivation, which is essential for fertilization. Male mice lacking sperm\u2010specific 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 GSK3\u03b1 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\u2010selective inhibitor of GSK3\u03b1, BRD0705, also inhibited fertilization of eggs in vitro. Interrelated functions of GSK3\u03b1 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.<\/jats:p>","DOI":"10.1096\/fj.201902163r","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T08:22:53Z","timestamp":1575015773000},"page":"1247-1269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs"],"prefix":"10.1096","volume":"34","author":[{"given":"Souvik","family":"Dey","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Kent State University Kent OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Eisa","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Kent State University Kent OH 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