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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
Status neindexováno Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
R15 HD110863
NICHD NIH HHS - United States
NLK
Directory of Open Access Journals
od 2013
Free Medical Journals
od 2013
PubMed Central
od 2013
Europe PubMed Central
od 2013
Open Access Digital Library
od 2013-01-01
Open Access Digital Library
od 2013-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2013
- Publikační typ
- časopisecké články MeSH
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.
Department of Developmental Pathology Institute of Pathology University Hospital Bonn Bonn Germany
Department of Human Genetics University of Michigan Ann Arbor MI United States
Department of Physiology Faculty of Science Charles University Prague Czechia
Department of Zoology Faculty of Science Charles University Prague Czechia
Citace poskytuje Crossref.org
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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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