{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:54:20Z","timestamp":1777420460078,"version":"3.51.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HD107333-01"],"award-info":[{"award-number":["HD107333-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"crossref","award":["BT\/RLF\/Re-entry\/08\/2019"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/08\/2019"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:sec>\n                    <jats:title>In brief<\/jats:title>\n                    <jats:p>Protein phosphatase 1 catalytic subunit gamma isoform 2 (PP1\u03b32) is a unique phosphatase expressed only in mammalian testes and sperm cells. The PP1\u03b32 isoform is indispensable for sperm motility and fertility and cannot be replaced by the PP1\u03b31 isoform for these functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The serine\u2013threonine phosphatase has four paralogs \u2013 PP1\u03b1, PP1\u03b2, PP1\u03b31 and PP1\u03b32 \u2013 encoded by three genes,\n                      <jats:italic>Ppp1ca<\/jats:italic>\n                      ,\n                      <jats:italic>Ppp1cb<\/jats:italic>\n                      and\n                      <jats:italic>Ppp1cc<\/jats:italic>\n                      . Protein phosphatase PP1\u03b32, one of two isoforms of the gene\n                      <jats:italic>Ppp1cc<\/jats:italic>\n                      , is expressed in spermatogenic cells in the testes and sperm, while PP1\u03b31 is found in somatic cells. The two PP1\u03b3 isoforms, formed by alternate splicing that occurs only in mammals, are identical except at their C-termini. Global or testis-specific knockout of\n                      <jats:italic>Ppp1cc<\/jats:italic>\n                      in mice results in male infertility due to disrupted spermiation and mid-to-late spermiogenesis. Transgenic expression of PP1\u03b32, driven by a testis-specific promoter in differentiating spermatogenic cells, rescues spermatogenesis and fertility in the\n                      <jats:italic>Ppp1cc<\/jats:italic>\n                      -null mice. Why PP1\u03b32 is essential and present only in mammalian sperm is a mystery. We have generated a knock-in mouse where the\n                      <jats:italic>Ppp1cc<\/jats:italic>\n                      gene is edited to express only PP1\u03b31. Spermatogenesis was normal in knock-in mice. Testis-expressed PP1\u03b31 in the knock-in mice and PP1\u03b32 in the wild-type mice were incorporated in equal amounts into sperm. Sperm bearing PP1\u03b31 have reduced flagellar beat amplitude and motility, and male mice were severely sub-fertile. Although in the wild-type mice, PP1\u03b32 is present in both the head and tail, in the knock-in mice, PP1\u03b31 is absent in sperm heads, leading to an altered intra-sperm protein phosphatase landscape. Phosphoproteomic analysis of sperm proteins suggested a plausible molecular basis for compromised PP1\u03b31 functions: it identified GSK3\u03b1, a known substrate of PP1, to be dysregulated in knock-in sperm. This study provides a preliminary explanation for the isoform-specific requirement of PP1\u03b32 for male fertility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0256","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T14:02:25Z","timestamp":1733234545000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":1,"title":["PP1\u03b31 is unable to substitute for the mammal-specific PP1\u03b32 isoform to support male fertility and sperm function"],"prefix":"10.1093","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1799-5270","authenticated-orcid":true,"given":"Souvik","family":"Dey","sequence":"first","affiliation":[{"name":"Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1373-7638","authenticated-orcid":true,"given":"Wesam","family":"Nofal","sequence":"additional","affiliation":[{"name":"Biological Sciences, Kent State University, Kent, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron","family":"Brothag","sequence":"additional","affiliation":[{"name":"Biological Sciences, Kent State University, Kent, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustfa","family":"Kabi","sequence":"additional","affiliation":[{"name":"Biological Sciences, Kent State University, Kent, Ohio, USA"},{"name":"Department of Biology, University of Tabuk, Tabuk, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditi","family":"Khamamkar","sequence":"additional","affiliation":[{"name":"Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Choudhari","sequence":"additional","affiliation":[{"name":"Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivasan","family":"Vijayaraghavan","sequence":"additional","affiliation":[{"name":"Biological Sciences, Kent State University, Kent, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Int J Dev Biol","first-page":"415","article-title":"Puzzles of mammalian fertilization \u2013 and beyond","volume":"52","author":"Bedford JM","year":"2008","unstructured":"Bedford JM. 2008 Puzzles of mammalian fertilization \u2013 and beyond. 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