Linker histones stimulate HSPA2 ATPase activity through NASP binding and inhibit CDC2/Cyclin B1 complex formation during meiosis in the mouse.
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.
Alekseev
Oleg M
OM
Department of Cell & Developmental Biology and the Laboratories for Reproductive Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. alekseev@email.unc.edu
Richardson
Richard T
RT
O'Rand
Michael G
MG
D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins; D056744:Cyclin B1 / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism*; D013573:Synaptonemal Complex / Q000378:metabolism*
D001324:Autoantigens; C534700:Ccnb1 protein, mouse; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D018840:HSP70 Heat-Shock Proteins; D006657:Histones; C490434:Hspa2 protein, mouse; D009687:Nuclear Proteins; C067535:Nasp protein, mouse; D016203:CDC2 Protein Kinase