Protamine 2 deficiency results in Septin 12 abnormalities
There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts wit...
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1447630/full |
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| author | Ondrej Sanovec Ondrej Sanovec Michaela Frolikova Veronika Kraus Jana Vondrakova Maryam Qasemi Daniela Spevakova Ondrej Simonik Lindsay Moritz Drew Lewis Caswell Frantisek Liska Lukas Ded Jiri Cerny Tomer Avidor-Reiss Tomer Avidor-Reiss Saher Sue Hammoud Hubert Schorle Pavla Postlerova Klaus Steger Katerina Komrskova Katerina Komrskova |
| author_facet | Ondrej Sanovec Ondrej Sanovec Michaela Frolikova Veronika Kraus Jana Vondrakova Maryam Qasemi Daniela Spevakova Ondrej Simonik Lindsay Moritz Drew Lewis Caswell Frantisek Liska Lukas Ded Jiri Cerny Tomer Avidor-Reiss Tomer Avidor-Reiss Saher Sue Hammoud Hubert Schorle Pavla Postlerova Klaus Steger Katerina Komrskova Katerina Komrskova |
| author_sort | Ondrej Sanovec |
| collection | DOAJ |
| description | There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associated with sperm motility. Septin 12 has several isoforms, and we show, that in the Prm2−/− sperm, the short one (Mw 36 kDa) is mis-localized, while two long isoforms (Mw 40 and 41 kDa) are unexpectedly lost in Prm2−/− sperm chromatin-bound protein fractions. Septin 12 co-immunoprecipitated with Protamine 2 in the testicular cell lysate of WT mice and with Lamin B1/2/3 in co-transfected HEK cells despite we did not observe changes in Lamin B2/B3 proteins or SUN4 expression in Prm2−/− testes. Furthermore, the Prm2−/− sperm have on average a smaller sperm nucleus and aberrant acrosome biogenesis. In humans, patients with low sperm motility (asthenozoospermia) have imbalanced histone–protamine 1/2 ratio, modified levels of cytoskeletal proteins and we detected retained Septin 12 isoforms (Mw 40 and 41 kDa) in the sperm membrane, chromatin-bound and tubulin/mitochondria protein fractions. In conclusion, our findings present potential interaction between Septin 12 and Protamine 2 or Lamin B2/3 and describe a new connection between their expression and localization, contributing likely to low sperm motility and morphological abnormalities. |
| format | Article |
| id | doaj-art-01217af291054fa2bce783d7e7012b4f |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-01217af291054fa2bce783d7e7012b4f2025-08-20T02:11:38ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-10-011210.3389/fcell.2024.14476301447630Protamine 2 deficiency results in Septin 12 abnormalitiesOndrej Sanovec0Ondrej Sanovec1Michaela Frolikova2Veronika Kraus3Jana Vondrakova4Maryam Qasemi5Daniela Spevakova6Ondrej Simonik7Lindsay Moritz8Drew Lewis Caswell9Frantisek Liska10Lukas Ded11Jiri Cerny12Tomer Avidor-Reiss13Tomer Avidor-Reiss14Saher Sue Hammoud15Hubert Schorle16Pavla Postlerova17Klaus Steger18Katerina Komrskova19Katerina Komrskova20Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaDepartment of Physiology, Faculty of Science, Charles University, Prague, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaDepartment of Human Genetics, University of Michigan, Ann Arbor, MI, United StatesDepartment of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United StatesInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaLaboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology Czech Academy of Sciences, BIOCEV, Vestec, CzechiaDepartment of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United StatesDepartment of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United StatesDepartment of Human Genetics, University of Michigan, Ann Arbor, MI, United StatesDepartment of Developmental Pathology, Institute of Pathology, University Hospital Bonn, Bonn, GermanyLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, CzechiaClinic of Urology, Paediatric Urology and Andrology, Molecular Andrology, Justus Liebig University of Giessen, Giessen, GermanyLaboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia0Department of Zoology, Faculty of Science, Charles University, Prague, CzechiaThere is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associated with sperm motility. Septin 12 has several isoforms, and we show, that in the Prm2−/− sperm, the short one (Mw 36 kDa) is mis-localized, while two long isoforms (Mw 40 and 41 kDa) are unexpectedly lost in Prm2−/− sperm chromatin-bound protein fractions. Septin 12 co-immunoprecipitated with Protamine 2 in the testicular cell lysate of WT mice and with Lamin B1/2/3 in co-transfected HEK cells despite we did not observe changes in Lamin B2/B3 proteins or SUN4 expression in Prm2−/− testes. Furthermore, the Prm2−/− sperm have on average a smaller sperm nucleus and aberrant acrosome biogenesis. In humans, patients with low sperm motility (asthenozoospermia) have imbalanced histone–protamine 1/2 ratio, modified levels of cytoskeletal proteins and we detected retained Septin 12 isoforms (Mw 40 and 41 kDa) in the sperm membrane, chromatin-bound and tubulin/mitochondria protein fractions. In conclusion, our findings present potential interaction between Septin 12 and Protamine 2 or Lamin B2/3 and describe a new connection between their expression and localization, contributing likely to low sperm motility and morphological abnormalities.https://www.frontiersin.org/articles/10.3389/fcell.2024.1447630/fullProtamine 2 deficiencySeptin 12spermasthenozoospermiasperm immotilityannulus |
| spellingShingle | Ondrej Sanovec Ondrej Sanovec Michaela Frolikova Veronika Kraus Jana Vondrakova Maryam Qasemi Daniela Spevakova Ondrej Simonik Lindsay Moritz Drew Lewis Caswell Frantisek Liska Lukas Ded Jiri Cerny Tomer Avidor-Reiss Tomer Avidor-Reiss Saher Sue Hammoud Hubert Schorle Pavla Postlerova Klaus Steger Katerina Komrskova Katerina Komrskova Protamine 2 deficiency results in Septin 12 abnormalities Frontiers in Cell and Developmental Biology Protamine 2 deficiency Septin 12 sperm asthenozoospermia sperm immotility annulus |
| title | Protamine 2 deficiency results in Septin 12 abnormalities |
| title_full | Protamine 2 deficiency results in Septin 12 abnormalities |
| title_fullStr | Protamine 2 deficiency results in Septin 12 abnormalities |
| title_full_unstemmed | Protamine 2 deficiency results in Septin 12 abnormalities |
| title_short | Protamine 2 deficiency results in Septin 12 abnormalities |
| title_sort | protamine 2 deficiency results in septin 12 abnormalities |
| topic | Protamine 2 deficiency Septin 12 sperm asthenozoospermia sperm immotility annulus |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1447630/full |
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