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Protamine 2 deficiency results in Septin 12 abnormalities

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    0601325 - BTÚ 2025 RIV CH eng J - Journal Article
    Šanovec, Ondřej - Frolíková, Michaela - Kraus, Veronika - Vondráková, Jana - Qasemi, Maryam - Spěváková, Daniela - Šimoník, Ondřej - Moritz, L. - Caswell, D. L. - Liška, F. - Děd, Lukáš - Černý, Jiří - Avidor-Reiss, T. - Hammoud, S. S. - Schorle, H. - Postlerová, Pavla - Steger, K. - Komrsková, Kateřina
    Protamine 2 deficiency results in Septin 12 abnormalities.
    Frontiers in Cell and Developmental Biology. Roč. 12, OCT 25 2024 (2024), č. článku 1447630. ISSN 2296-634X. E-ISSN 2296-634X
    R&D Projects: GA ČR(CZ) GA23-06591S; GA ČR(CZ) GC20-20217J; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) EF16_013/0001775; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) LM2023050
    Institutional support: RVO:86652036
    Keywords : sperm * mouse * Lamin * annulus * asthenozoospermia * organization * DNA, * sperm immotility
    OECD category: Reproductive biology (medical aspects to be 3)
    Impact factor: 4.6, year: 2023 ; AIS: 1.319, rok: 2023
    Method of publishing: Open access
    Result website:
    https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1447630/fullDOI: https://doi.org/10.3389/fcell.2024.1447630

    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.
    Permanent Link: https://hdl.handle.net/11104/0359058
     
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    Protamine 2 deficiency results in Septin 12 abnormalities.pdf05.5 MBAuthor´s preprintopen-access
     
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