Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
| Autor: | Peter B. Moens, Yoichi Arai, Tracy McQuire, Hitoshi Okada, Edyta Marcon, Toru Sasaki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
RAD51 Apoptosis Biology Cell Line Male infertility Mice 03 medical and health sciences 0302 clinical medicine Meiosis Report HSPA2 Homologous chromosome medicine Animals Humans HSP70 Heat-Shock Proteins Nuclear protein Polyubiquitin Spermatogenesis Research Articles 030304 developmental biology 0303 health sciences Synaptonemal Complex Nuclear Proteins Cell Biology medicine.disease Spermatozoa Cell biology Synaptonemal complex Organ Specificity 030220 oncology & carcinogenesis Thermodynamics Carrier Proteins Protein Processing Post-Translational Molecular Chaperones Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200802113 |
| Popis: | Meiosis is critical for sexual reproduction. During meiosis, the dynamics and integrity of homologous chromosomes are tightly regulated. The genetic and molecular mechanisms governing these processes in vivo, however, remain largely unknown. In this study, we demonstrate that Bat3/Scythe is essential for survival and maintenance of male germ cells (GCs). Targeted inactivation of Bat3/Scythe in mice results in widespread apoptosis of meiotic male GCs and complete male infertility. Pachytene spermatocytes exhibit abnormal assembly and disassembly of synaptonemal complexes as demonstrated by abnormal SYCP3 staining and sustained γ-H2AX and Rad51/replication protein A foci. Further investigation revealed that a testis-specific protein, Hsp70-2/HspA2, is absent in Bat3-deficient male GCs at any stage of spermatogenesis; however, Hsp70-2 transcripts are expressed at normal levels. We found that Bat3 deficiency induces polyubiquitylation and subsequent degradation of Hsp70-2. Inhibition of proteasomal degradation restores Hsp70-2 protein levels. Our findings identify Bat3 as a critical regulator of Hsp70-2 in spermatogenesis, thereby providing a possible molecular target in idiopathic male infertility. |
| Databáze: | OpenAIRE |
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