| First Author | Dudiki T | Year | 2019 |
| Journal | Biol Reprod | Volume | 100 |
| Issue | 3 | Pages | 721-736 |
| PubMed ID | 30379985 | Mgi Jnum | J:276787 |
| Mgi Id | MGI:6316744 | Doi | 10.1093/biolre/ioy225 |
| Citation | Dudiki T, et al. (2019) The protein phosphatase isoform PP1gamma1 substitutes for PP1gamma2 to support spermatogenesis but not normal sperm function and fertility. Biol Reprod 100(3):721-736 |
| abstractText | Four isoforms of serine/threonine phosphatase type I, PP1alpha, PP1beta, PP1gamma1, and PP1gamma2, are derived from three genes. The PP1gamma1 and PP1gamma2 isoforms are alternately spliced transcripts of the protein phosphatase 1 catalytic subunit gamma gene (Ppp1cc). While PP1gamma1 is ubiquitous in somatic cells, PP1gamma2 is expressed exclusively in testicular germ cells and sperm. Ppp1cc knockout male mice (-/-), lacking both PP1gamma1 and PP1gamma2, are sterile due to impaired sperm morphogenesis. Fertility and normal sperm function can be restored by transgenic expression of PP1gamma2 alone in testis of Ppp1cc (-/-) mice. The purpose of this study was to determine whether the PP1gamma1 isoform is functionally equivalent to PP1gamma2 in supporting spermatogenesis and male fertility. Significant levels of transgenic PP1gamma1 expression occurred only when the transgene lacked a 1-kb 3UTR region immediately following the stop codon of the PP1gamma1 transcript. PP1gamma1 was also incorporated into sperm at levels comparable to PP1gamma2 in sperm from wild-type mice. Spermatogenesis was restored in mice expressing PP1gamma1 in the absence of PP1gamma2. However, males from the transgenic rescue lines were subfertile. Sperm from the PP1gamma1 rescue mice were unable to fertilize eggs in vitro. Intrasperm localization of PP1gamma1 and the association of the protein regulators of the phosphatase were altered in epididymal sperm in transgenic PP1gamma1 compared to PP1gamma2. Thus, the ubiquitous isoform PP1gamma1, not normally expressed in differentiating germ cells, could replace PP1gamma2 to support spermatogenesis and spermiation. However, PP1gamma2, which is the PP1 isoform in mammalian sperm, has an isoform-specific role in supporting normal sperm function and fertility. |
