scholarly journals Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice

Reproduction ◽  
2017 ◽  
Vol 154 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Kasane Kishi ◽  
Aya Uchida ◽  
Hinako M Takase ◽  
Hitomi Suzuki ◽  
Masamichi Kurohmaru ◽  
...  
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Apoptotic Cell ◽  
Cell Lineage ◽  
Conditional Knockout ◽  
Spermatogenic Cells ◽  
Male Mice ◽  
Conditional Deletion ◽  
Fat Facets

USP9X (ubiquitin-specific peptidase 9, X chromosome) is the mammalian orthologue of Drosophila deubiquitinase fat facets that was previously shown to regulate the maintenance of the germ cell lineage partially through stabilizing Vasa, one of the widely conserved factors crucial for gametogenesis. Here, we demonstrate that USP9X is expressed in the gonocytes and spermatogonia in mouse testes from newborn to adult stages. By using Vasa-Cre mice, germ cell-specific conditional deletion of Usp9x from the embryonic stage showed no abnormality in the developing testes by 1 week and no appreciable defects in the undifferentiated and differentiating spermatogonia at postnatal and adult stages. Interestingly, after 2 weeks, Usp9x-null spermatogenic cells underwent apoptotic cell death at the early spermatocyte stage, and then, caused subsequent aberrant spermiogenesis, which resulted in a complete infertility of Usp9x conditional knockout male mice. These data provide the first evidence of the crucial role of the spermatogonial USP9X during transition from the mitotic to meiotic phases and/or maintenance of early meiotic phase in Usp9x conditional knockout testes.

scholarly journals Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice

2011 ◽  
Vol 22 (10) ◽  
pp. 1766-1779 ◽  
Author(s):  
Karina Kaczmarek ◽  
Maja Studencka ◽  
Andreas Meinhardt ◽  
Krzysztof Wieczerzak ◽  
Sven Thoms ◽  
...  
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Specific Gene ◽  
Male Mice ◽  
Terminal Part ◽  
Male Germ Cells ◽  
Germ Cell Apoptosis ◽  
Induced Apoptosis

 Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells’ apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3.

Mixed-ligand copper(ii) Schiff base complexes: the vital role of co-ligands in DNA/protein interactions and cytotoxicity

2017 ◽  
Vol 41 (3) ◽  
pp. 1267-1283 ◽  
Author(s):  
Sellamuthu Kathiresan ◽  
Subramanian Mugesh ◽  
Jamespandi Annaraj ◽  
Maruthamuthu Murugan
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
Schiff Base ◽  
Protein Interactions ◽  
Apoptotic Cell ◽  
Vital Role ◽  
Mixed Ligand ◽  
Schiff Base Complexes ◽  
Antibacterial Mechanism

Four new mixed-ligand copper(ii) complexes display an antibacterial mechanism of cell death via cell-wall rupture and cytotoxicity via apoptotic cell death.

scholarly journals Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 1011-1022 ◽  
Author(s):  
T.L. Gumienny ◽  
E. Lambie ◽  
E. Hartwieg ◽  
H.R. Horvitz ◽  
M.O. Hengartner
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Somatic Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Mapk Pathway ◽  
Apoptotic Cell ◽  
C Elegans ◽  
Pathway Activation

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

scholarly journals Caspase-9 cleavage, do you need it?

2007 ◽  
Vol 405 (1) ◽  
Author(s):  
Davina Twiddy ◽  
Kelvin Cain
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Caspase 9 ◽  
Autocatalytic Cleavage ◽  
Downstream Effector ◽  
Apoptosis Inhibition ◽  
Biochemical Journal ◽  
Effector Caspase ◽  
Effector Caspases

Caspase-9, which is activated by association with the Apaf-1 (apoptotic protease-activating factor-1) apoptosome complex, cleaves and activates the downstream effector caspases-3 and -7, thereby executing the caspase-cascade and cell-death programme. Although caspase-9 does not need to be cleaved to be active, apoptotic cell death is always accompanied by autocatalytic cleavage and by further downstream effector caspase-dependent cleavage of caspase-9. In this issue of the Biochemical Journal, Denault and co-workers evaluate the role of caspase-3-dependent cleavage of caspase-9 and conclude that this mechanism mainly serves to enhance apoptosis by alleviating XIAP (X-linked inhibitor of apoptosis) inhibition of the apical caspase.

Sign in / Sign up

Export Citation Format

Share Document