| First Author | Bhattacharjee R | Year | 2018 |
| Journal | Biol Reprod | Volume | 99 |
| Issue | 2 | Pages | 384-394 |
| PubMed ID | 29385396 | Mgi Jnum | J:264439 |
| Mgi Id | MGI:6194496 | Doi | 10.1093/biolre/ioy020 |
| Citation | Bhattacharjee R, et al. (2018) Isoform-specific requirement for GSK3alpha in sperm for male fertility. Biol Reprod 99(2):384-394 |
| abstractText | Glycogen synthase kinase 3 (GSK3) is a highly conserved protein kinase regulating key cellular functions. Its two isoforms, GSK3alpha and GSK3beta, are encoded by distinct genes. In most tissues the two isoforms are functionally interchangeable, except in the developing embryo where GSK3beta 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 GSK3alpha, but not GSK3beta, in developing testicular germ cells in mice results in male infertility. Mice lacking one allele each of GSK3alpha and GSK3beta are fertile. Despite overlapping expression and localization in differentiating spermatids, GSK3beta does not substitute for GSK3alpha. Loss of GSK3alpha impairs sperm hexokinase activity resulting in low ATP levels. Net adenine nucleotide levels in caudal sperm lacking GSK3alpha resemble immature caput epididymal sperm. Changes in the association of the protein phosphatase PP1gamma2 with its protein interactors occurring during epididymal sperm maturation is impaired in sperm lacking GSK3alpha. The isoform-specific requirement for GSK3alpha is likely due to its specific binding partners in the sperm principal piece. Testis and sperm are unique in their specific requirement of GSK3alpha for normal function and male fertility. |
