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

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 essentia...

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Autores principales: Sasaki, Toru, Marcon, Edyta, McQuire, Tracy, Arai, Yoichi, Moens, Peter B., Okada, Hitoshi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500131/
https://www.ncbi.nlm.nih.gov/pubmed/18678708
http://dx.doi.org/10.1083/jcb.200802113
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author Sasaki, Toru
Marcon, Edyta
McQuire, Tracy
Arai, Yoichi
Moens, Peter B.
Okada, Hitoshi
author_facet Sasaki, Toru
Marcon, Edyta
McQuire, Tracy
Arai, Yoichi
Moens, Peter B.
Okada, Hitoshi
author_sort Sasaki, Toru
collection PubMed
description 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.
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spelling pubmed-25001312009-02-11 Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis Sasaki, Toru Marcon, Edyta McQuire, Tracy Arai, Yoichi Moens, Peter B. Okada, Hitoshi J Cell Biol Research Articles 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. The Rockefeller University Press 2008-08-11 /pmc/articles/PMC2500131/ /pubmed/18678708 http://dx.doi.org/10.1083/jcb.200802113 Text en © 2008 Sasaki et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Sasaki, Toru
Marcon, Edyta
McQuire, Tracy
Arai, Yoichi
Moens, Peter B.
Okada, Hitoshi
Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
title Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
title_full Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
title_fullStr Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
title_full_unstemmed Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
title_short Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis
title_sort bat3 deficiency accelerates the degradation of hsp70-2/hspa2 during spermatogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500131/
https://www.ncbi.nlm.nih.gov/pubmed/18678708
http://dx.doi.org/10.1083/jcb.200802113
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