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Protamine 2 deficiency results in Septin 12 abnormalities

O. Sanovec, M. Frolikova, V. Kraus, J. Vondrakova, M. Qasemi, D. Spevakova, O. Simonik, L. Moritz, DL. Caswell, F. Liska, L. Ded, J. Cerny, T. Avidor-Reiss, SS. Hammoud, H. Schorle, P. Postlerova, K. Steger, K. Komrskova

. 2024 ; 12 (-) : 1447630. [pub] 20241025

Status neindexováno Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25002286

Grantová podpora
R15 HD110863 NICHD NIH HHS - United States

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.

Citace poskytuje Crossref.org

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$a Protamine 2 deficiency results in Septin 12 abnormalities / $c O. Sanovec, M. Frolikova, V. Kraus, J. Vondrakova, M. Qasemi, D. Spevakova, O. Simonik, L. Moritz, DL. Caswell, F. Liska, L. Ded, J. Cerny, T. Avidor-Reiss, SS. Hammoud, H. Schorle, P. Postlerova, K. Steger, K. Komrskova
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$a 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.
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$a Frolikova, Michaela $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Kraus, Veronika $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Vondrakova, Jana $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Qasemi, Maryam $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Spevakova, Daniela $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Simonik, Ondrej $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Moritz, Lindsay $u Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States
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$a Caswell, Drew Lewis $u Department of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United States
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$a Liska, Frantisek $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
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$a Ded, Lukas $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Cerny, Jiri $u Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Avidor-Reiss, Tomer $u Department of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United States $u Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United States
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$a Hammoud, Saher Sue $u Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States
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$a Schorle, Hubert $u Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, Bonn, Germany
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$a Postlerova, Pavla $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia
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$a Steger, Klaus $u Clinic of Urology, Paediatric Urology and Andrology, Molecular Andrology, Justus Liebig University of Giessen, Giessen, Germany
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$a Komrskova, Katerina $u Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia $u Department of Zoology, Faculty of Science, Charles University, Prague, Czechia
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