Role of heat shock protein HSP70-2 in spermatogenesis.
The HSP70 heat-shock proteins are molecular chaperones that assist other proteins in their folding, transport and assembly into complexes. Most of these proteins are either constitutively expressed or their expression is induced by heat shock and other stresses. However, two members of the Hsp70 family (HSP70-2 and HSC70T in mice) are regulated developmentally and expressed specifically in spermatogenic cells. The HSP70-2 protein is synthesized during the meiotic phase of spermatogenesis and is abundant in pachytene spermatocytes. The knockout approach was used to determine whether HSP70-2 is a chaperone for proteins involved in meiosis. Male mice lacking HSP70-2 were infertile while females lacking HSP70-2 were fertile. Spermatogenic cell development was arrested in prophase of meiosis I at the G2-M-phase transition and late pachytene spermatocytes were eliminated by apoptosis, resulting in an absence of spermatids. HSP70-2 is required for Cdc2 to form a heterodimer with cyclin B1, suggesting that it is a chaperone necessary for the progression of meiosis in the germ cells of male mice. HSP70-2 is also associated with the synaptonemal complex and desynapsis is disrupted in male mice lacking this protein. Homologues of HSP70-2 are present in the testes of many animals, suggesting that the role of this spermatogenic cell chaperone is conserved across phyla.
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
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D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D012671:Seminiferous Tubules / Q000166:cytology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology; D013573:Synaptonemal Complex / Q000502:physiology
D018797:Cell Cycle Proteins; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; C490434:Hspa2 protein, mouse