Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis

Author:

Sasaki Toru1,Marcon Edyta2,McQuire Tracy1,Arai Yoichi3,Moens Peter B.2,Okada Hitoshi145

Affiliation:

1. The Campbell Family Institute for Breast Cancer Research

2. Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada

3. Department of Urology, Tohoku University, School of Medicine, Aoba-ku, Sendai 980-8574, Japan

4. Division of Signaling Biology, Ontario Cancer Institute, University Health Network,

5. Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada

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 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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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