Protamine 2 deficiency results in Septin 12 abnormalities.
| Title: | Protamine 2 deficiency results in Septin 12 abnormalities. |
|---|---|
| Authors: | Sanovec O; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Department of Physiology, Faculty of Science, Charles University, Prague, Czechia.; Frolikova M; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Kraus V; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Vondrakova J; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Qasemi M; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Spevakova D; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Simonik O; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Moritz L; Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States.; Caswell DL; Department of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United States.; Liska F; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.; Ded L; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Cerny J; Laboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Avidor-Reiss T; Department of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United States.; Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United States.; Hammoud SS; Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States.; Schorle H; Department of Developmental Pathology, Institute of Pathology, University Hospital Bonn, Bonn, Germany.; Postlerova P; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Steger K; Clinic of Urology, Paediatric Urology and Andrology, Molecular Andrology, Justus Liebig University of Giessen, Giessen, Germany.; Komrskova K; Laboratory of Reproductive Biology, Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Czechia.; Department of Zoology, Faculty of Science, Charles University, Prague, Czechia. |
| Source: | Frontiers in cell and developmental biology [Front Cell Dev Biol] 2024 Oct 25; Vol. 12, pp. 1447630. Date of Electronic Publication: 2024 Oct 25 (Print Publication: 2024). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101630250 Publication Model: eCollection Cited Medium: Print ISSN: 2296-634X (Print) Linking ISSN: 2296634X NLM ISO Abbreviation: Front Cell Dev Biol Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Lausanne : Frontiers Media S.A., [2013]- |
| Abstract: | 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.; (Copyright © 2024 Sanovec, Frolikova, Kraus, Vondrakova, Qasemi, Spevakova, Simonik, Moritz, Caswell, Liska, Ded, Cerny, Avidor-Reiss, Hammoud, Schorle, Postlerova, Steger and Komrskova.) |
| Competing Interests: | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Comments: | Update of: bioRxiv. 2024 May 30:2024.05.28.596175. doi: 10.1101/2024.05.28.596175.. (PMID: 38854089) |
| References: | Nat Rev Mol Cell Biol. 2012 Feb 08;13(3):183-94. (PMID: 22314400); Spermatogenesis. 2011 Oct;1(4):298-302. (PMID: 22332113); Fertil Steril. 2011 Jan;95(1):363-5. (PMID: 20801438); J Biol Chem. 1993 May 15;268(14):10553-7. (PMID: 8486708); Reproduction. 2022 Jul 26;164(3):R57-R74. (PMID: 35900356); Nat Rev Urol. 2016 Oct;13(10):584-95. (PMID: 27578043); Hum Reprod Update. 2006 Jul-Aug;12(4):417-35. (PMID: 16581810); Cells. 2022 Apr 01;11(7):. (PMID: 35406752); Epigenetics Chromatin. 2014 Jan 20;7(1):2. (PMID: 24443974); J Cell Biol. 1982 May;93(2):298-305. (PMID: 7096440); PLoS One. 2012;7(3):e34011. (PMID: 22479503); Sci Rep. 2016 Nov 11;6:36764. (PMID: 27833122); EMBO J. 1993 Jan;12(1):97-106. (PMID: 8094052); Histochemistry. 1977 Oct 3;54(1):1-7. (PMID: 914658); Eur J Cell Biol. 2005 Jul;84(7):649-62. (PMID: 16106909); Nucleic Acids Res. 1990 Mar 11;18(5):1249-54. (PMID: 2320417); Nature. 2013 May 16;497(7449):332-7. (PMID: 23575631); Adv Biol Regul. 2019 Aug;73:100635. (PMID: 31420262); J Cell Biol. 2002 Oct 28;159(2):255-66. (PMID: 12403812); Hum Reprod. 2005 Jan;20(1):9-11. (PMID: 15471925); J Urol. 2008 Dec;180(6):2706-9. (PMID: 18951558); PLoS One. 2015 Mar 16;10(3):e0120722. (PMID: 25775403); Cytometry A. 2005 May;65(1):40-9. (PMID: 15779065); Sci Rep. 2016 Sep 26;6:33714. (PMID: 27666019); J Phys Chem B. 2021 Apr 1;125(12):3032-3044. (PMID: 33754735); Front Genet. 2019 Oct 08;10:962. (PMID: 31649732); Dev Biol. 2015 Nov 15;407(2):321-30. (PMID: 26417726); Hum Reprod. 2009 Jun;24(6):1296-303. (PMID: 19221096); Nat Commun. 2024 Jan 2;15(1):117. (PMID: 38168044); Biol Reprod. 1991 Apr;44(4):569-74. (PMID: 2043729); Nat Rev Urol. 2012 Nov;9(11):609-19. (PMID: 23045264); Mol Reprod Dev. 2002 Apr;61(4):519-27. (PMID: 11891924); Int J Androl. 2008 Dec;31(6):537-45. (PMID: 18298569); Biol Chem Hoppe Seyler. 1986 Jun;367(6):515-22. (PMID: 3527226); J Cell Biol. 2023 Mar 6;222(3):. (PMID: 36562751); Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844); Protein Pept Lett. 2011 Aug;18(8):772-7. (PMID: 21443494); Int J Mol Sci. 2020 Nov 28;21(23):. (PMID: 33260574); Cells. 2020 Jul 27;9(8):. (PMID: 32727081); Biol Rev Camb Philos Soc. 2019 Aug;94(4):1195-1219. (PMID: 30701647); Dev Cell. 2005 Mar;8(3):343-52. (PMID: 15737930); Int J Mol Sci. 2021 Jan 25;22(3):. (PMID: 33503798); J Androl. 2003 May-Jun;24(3):438-47. (PMID: 12721220); Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2202803119. (PMID: 36475946); Nature. 2009 Jul 23;460(7254):473-8. (PMID: 19525931); Biol Reprod. 2004 May;70(5):1400-10. (PMID: 14724135); Reproduction. 2019 Feb;157(2):R53-R72. (PMID: 30576284); Reprod Med Biol. 2021 Aug 11;20(4):537-542. (PMID: 34646082); Mol Cell Endocrinol. 2020 Dec 1;518:110987. (PMID: 32810575); Exp Cell Res. 2005 Jul 15;307(2):285-91. (PMID: 15950617); Am J Pathol. 2009 May;174(5):1857-68. (PMID: 19359518); J Struct Biol. 2005 Oct;152(1):36-51. (PMID: 16182563); PLoS Genet. 2022 Jun 28;18(6):e1010272. (PMID: 35763544); Nat Struct Mol Biol. 2013 Jul;20(7):868-75. (PMID: 23770822); Biol Cell. 1993;78(1-2):53-62. (PMID: 8220227); Hum Reprod. 2017 Mar 1;32(3):514-522. (PMID: 28104696); Front Cell Dev Biol. 2022 Sep 06;10:972017. (PMID: 36158203); Eur J Biochem. 1993 Jun 1;214(2):609-15. (PMID: 8513810); Asian-Australas J Anim Sci. 2018 Nov;31(11):1729-1737. (PMID: 29642674); J Cell Sci. 2023 Apr 1;136(7):. (PMID: 36825599); Hum Reprod. 2017 Aug 1;32(8):1574-1582. (PMID: 28854581); Biochim Biophys Acta. 1969;188(2):353-6. (PMID: 5823033); Int J Mol Sci. 2019 Mar 07;20(5):. (PMID: 30866452); Hum Reprod. 2013 Apr;28(4):969-78. (PMID: 23340056); Mol Biol Cell. 2003 Nov;14(11):4628-40. (PMID: 14551252); Hum Mutat. 2012 Apr;33(4):710-9. (PMID: 22275165); Cytometry A. 2014 Jun;85(6):556-65. (PMID: 24664803); Nat Protoc. 2013 Dec;8(12):2449-70. (PMID: 24232248); Elife. 2023 Feb 15;12:. (PMID: 36790165); PLoS Genet. 2017 Mar 27;13(3):e1006631. (PMID: 28346465); Science. 1987 May 22;236(4804):962-4. (PMID: 3576213) |
| Grant Information: | R15 HD110863 United States HD NICHD NIH HHS |
| Contributed Indexing: | Keywords: Protamine 2 deficiency; Septin 12; annulus; asthenozoospermia; sperm; sperm immotility |
| Entry Date(s): | Date Created: 20241111 Latest Revision: 20241119 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11543461 |
| DOI: | 10.3389/fcell.2024.1447630 |
| PMID: | 39524225 |
| Database: | MEDLINE |
Journal Article