The protein phosphatase isoform PP1γ 1 substitutes for PP1γ 2 to support spermatogenesis but not normal sperm function and fertility

• Published in: Biology of reproduction Vol. 100; no. 3; pp. 721 - 736
• Main Authors: Dudiki, Tejasvi, Joudeh, Nidaa, Sinha, Nilam, Goswami, Suranjana, Eisa, Alaa, Kline, Douglas, Vijayaraghavan, Srinivasan
• Format: Journal Article
• Language: English
• Published: Society for the Study of Reproduction 01.03.2019
• Subjects: male fertility; protein phosphatases; RESEARCH ARTICLE; spermatogenesis; transgenic rescue
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioy225

Four isoforms of serine/threonine phosphatase type I, PP1α, PP1β, PP1γ 1, and PP1γ 2, are derived from three genes. The PP1γ 1 and PP1γ 2 isoforms are alternately spliced transcripts of the protein phosphatase 1 catalytic subunit gamma gene (Ppp1cc). While PP1γ 1 is ubiquitous in somatic cells, PP1γ 2 is expressed exclusively in testicular germ cells and sperm. Ppp1cc knockout male mice (–/–), lacking both PP1γ 1 and PP1γ 2, are sterile due to impaired sperm morphogenesis. Fertility and normal sperm function can be restored by transgenic expression of PP1γ 2 alone in testis of Ppp1cc (–/–) mice. The purpose of this study was to determine whether the PP1γ 1 isoform is functionally equivalent to PP1γ 2 in supporting spermatogenesis and male fertility. Significant levels of transgenic PP1γ 1 expression occurred only when the transgene lacked a 1-kb 3′UTR region immediately following the stop codon of the PP1γ 1 transcript. PP1γ 1 was also incorporated into sperm at levels comparable to PP1γ 2 in sperm from wild-type mice. Spermatogenesis was restored in mice expressing PP1γ 1 in the absence of PP1γ 2. However, males from the transgenic rescue lines were subfertile. Sperm from the PP1γ 1 rescue mice were unable to fertilize eggs in vitro. Intrasperm localization of PP1γ 1 and the association of the protein regulators of the phosphatase were altered in epididymal sperm in transgenic PP1γ 1 compared to PP1γ 2. Thus, the ubiquitous isoform PP1γ 1, not normally expressed in differentiating germ cells, could replace PP1γ 2 to support spermatogenesis and spermiation. However, PP1γ 2, which is the PP1 isoform in mammalian sperm, has an isoform-specific role in supporting normal sperm function and fertility. Summary Sentence PP1γ 1 can replace PP1γ2 in testis.