The molecular chaperone Hsp90alpha is required for meiotic progression of spermatocytes beyond pachytene in the mouse

Article Article scientifique Article The molecular chaperone Hsp90alpha is required for meiotic progression of spermatocytes beyond pachytene in the mouse eng 2010 author Grad Iwona 585158 author Cederroth Christopher 510564 author Walicki Joël Jonathan 680661 author Grey Corinne author Barluenga Badiola Sofia 810177 author Winssinger Nicolas 769664 author De Massy Bernard author Nef Serge 0000-0001-5462-0676 29062 author Picard Didier 0000-0001-8816-9668 26830 e15770 10.1371/journal.pone.0015770 21209834 1932-6203 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013136/pdf/pone.0015770.pdf The molecular chaperone Hsp90 has been found to be essential for viability in all tested eukaryotes, from the budding yeast to Drosophila. In mammals, two genes encode the two highly similar and functionally largely redundant isoforms Hsp90alpha and Hsp90beta. Although they are co-expressed in most if not all cells, their relative levels vary between tissues and during development. Since mouse embryos lacking Hsp90beta die at implantation, and despite the fact that Hsp90 inhibitors being tested as anti-cancer agents are relatively well tolerated, the organismic functions of Hsp90 in mammals remain largely unknown. We have generated mouse lines carrying gene trap insertions in the Hsp90alpha gene to investigate the global functions of this isoform. Surprisingly, mice without Hsp90alpha are apparently normal, with one major exception. Mutant male mice, whose Hsp90beta levels are unchanged, are sterile because of a complete failure to produce sperm. While the development of the male reproductive system appears to be normal, spermatogenesis arrests specifically at the pachytene stage of meiosis I. Over time, the number of spermatocytes and the levels of the meiotic regulators and Hsp90 interactors Hsp70-2, NASP and Cdc2 are reduced. We speculate that Hsp90alpha may be required to maintain and to activate these regulators and/or to disassemble the synaptonemal complex that holds homologous chromosomes together. The link between fertility and Hsp90 is further supported by our finding that an Hsp90 inhibitor that can cross the blood-testis barrier can partially phenocopy the genetic defects. Animals Blood-Testis Barrier Disease Progression Female HSP90 Heat-Shock Proteins/*metabolism Male Meiosis Mice Molecular Chaperones/*metabolism Mutation *Pachytene Stage Phenotype Spermatocytes/*cytology Spermatogenesis Spermatozoa/physiology Testis/*metabolism Dewey 570 Dewey 576.5 46 Département de biologie cellulaire 165 135 Département de médecine génétique et développement 21D false 448 Mécanismes moléculaires et génétiques du développement sexuel 778 PloS one 5 12 4b38391b-59c3-4392-8eb0-031d6b8a4a8c Article (Published version) Public file1.pdf 1215879 application/pdf CC BY openAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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The molecular chaperone Hsp90alpha is required for meiotic progression of spermatocytes beyond pachytene in the mouse	PloS one			2010	765	423

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Walicki, Joël Jonathan