Skip to main content

ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1447630
This article is part of the Research Topic Fertilization and Early Embryogenesis: From Research to Clinical Practice View all 13 articles

Protamine 2 Deficiency Results In Septin 12 Abnormalities

Provisionally accepted
Katerina Komrskova Katerina Komrskova 1,2*Ondrej Sanovec Ondrej Sanovec 1,3Michaela Frolikova Michaela Frolikova 1Veronika Kraus Veronika Kraus 1Jana Vondrakova Jana Vondrakova 1Maryam Qasemi Maryam Qasemi 1Daniela Spevakova Daniela Spevakova 1Ondřej Šimoník Ondřej Šimoník 1Lindsay Moritz Lindsay Moritz 4Drew L. Caswell Drew L. Caswell 5Frantisek Liska Frantisek Liska 6Lukas Ded Lukas Ded 1Jiri Cerny Jiri Cerny 7Tomer Avidor-Reiss Tomer Avidor-Reiss 5,8Sue Hammoud Sue Hammoud 4Hubert Schorle Hubert Schorle 9Pavla Postlerova Pavla Postlerova 1Klaus Steger Klaus Steger 10
  • 1 Laboratory of Reproductive Biology, Institute of Biotechnology (ASCR), Vestec, Czechia
  • 2 Department of Zoology, Faculty of Science, Charles University, Prague, Prague, Czechia
  • 3 Department of Physiology, Faculty of Science, Charles University, Prague, Prague, Czechia
  • 4 Department of Human Genetics, University of Michigan, Ann Arbor, United States
  • 5 Department of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, Ohio, United States
  • 6 Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Prague, Czechia
  • 7 Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology (ASCR), Vestec, Czechia
  • 8 Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, United States
  • 9 Institute of Pathology, University Hospital Bonn, Bonn, Germany
  • 10 Clinic of Urology, Paediatric Urology and Andrology, Molecular Andrology, Justus Liebig University of Giessen, Giessen, Germany

The final, formatted version of the article will be published soon.

    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 coimmunoprecipitated with Protamine 2 in the testicular cell lysate of WT mice and with Lamin B1/2/3 in cotransfected 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 histoneprotamine 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.

    Keywords: protamine 2 deficiency, septin 12, sperm, Asthenozoospermia, Immotility

    Received: 13 Jun 2024; Accepted: 27 Sep 2024.

    Copyright: © 2024 Komrskova, Sanovec, Frolikova, Kraus, Vondrakova, Qasemi, Spevakova, Šimoník, Moritz, Caswell, Liska, Ded, Cerny, Avidor-Reiss, Hammoud, Schorle, Postlerova and Steger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Katerina Komrskova, Laboratory of Reproductive Biology, Institute of Biotechnology (ASCR), Vestec, Czechia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.