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PMID:18678708

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Citation

Sasaki, T, Marcon, E, McQuire, T, Arai, Y, Moens, PB and Okada, H (2008) Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis. J. Cell Biol. 182:449-58

Abstract

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 gamma-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.

Links

PubMed PMC2500131 Online version:10.1083/jcb.200802113

Keywords

Animals; Apoptosis; Carrier Proteins/metabolism; Cell Line; HSP70 Heat-Shock Proteins/metabolism; Humans; Male; Mice; Molecular Chaperones; Nuclear Proteins/deficiency; Nuclear Proteins/metabolism; Organ Specificity; Polyubiquitin/metabolism; Protein Binding; Protein Processing, Post-Translational; Spermatogenesis; Spermatozoa/abnormalities; Spermatozoa/pathology; Synaptonemal Complex/metabolism; Thermodynamics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HSP72

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Z1R2

F

Seeded From UniProt

complete

MOUSE:BAG6

involved_in

GO:0032435: negative regulation of proteasomal ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAG6

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAG6

involved_in

GO:0007130: synaptonemal complex assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAG6

enables

GO:0030544: Hsp70 protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P17156

F

Seeded From UniProt

complete

MOUSE:BAG6

involved_in

GO:0050821: protein stabilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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