Linker Histones Stimulate HSPA2 ATPase Activity Through NASP Binding and Inhibit CDC2/Cyclin B1 Complex Formation During Meiosis in the Mouse1

• Published in: Biology of reproduction Vol. 81; no. 4; pp. 739 - 748
• Main Authors: Alekseev, Oleg M, Richardson, Richard T, O'Rand, Michael G
• Format: Journal Article
• Language: English
• Published: Society for the Study of Reproduction, Inc 01-10-2009
• Subjects: CDC2/cyclin B1; cell cycle; HSPA2; linker histones; meiosis; NASP; spermatogenesis; synamptonemal complex; testis
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.109.076497

In mammalian spermatocytes, cell division cycle protein 2 (CDC2)/cyclin B1 and the chaperone heat shock protein A2 (HSPA2) are required for the G2→M transition in prophase I. Here, we demonstrate that in primary spermatocytes, linker histone chaperone testis/embryo form of nuclear autoantigenic sperm protein (tNASP) binds the heat shock protein HSPA2, which localizes on the synaptonemal complex of spermatocytes. Significantly, the tNASP-HSPA2 complex binds linker histones and CDC2, forming a larger complex. We demonstrate that increasing amounts of tNASP favor tNASP-HSPA2-CDC2 complex formation. Binding of linker histones to tNASP significantly increases HSPA2 ATPase activity and the capacity of tNASP to bind HSPA2 and CDC2, precluding CDC2/cyclin B1 complex formation and, consequently, decreasing CDC2/cyclin B1 kinase activity. Linker histone binding to NASP controls the ability of HSPA2 to activate CDC2 for CDC2/cyclin B1 complex formation; therefore, tNASP's role is to provide the functional link between linker histones and cell cycle progression during meiosis.