Key role for cyclin-dependent kinases in the first and second meiotic divisions of rat spermatocytes.
In all systems examined so far, the G2/M phase transition is controlled by the M-phase promoting factor (MPF), a complex of cdc2 (CDK1) and cyclin B1. Histone H1 kinase activity and MPF components are present in pachytene spermatocytes (PS). However, it has not been demonstrated yet that direct inhibition of MPF activity prevents the G2/M transition in these cells. When roscovitine, a potent inhibitor of CDK1, CDK2, and CDK5 activities, was added to cocultures of PS with Sertoli cells, the number of both secondary spermatocytes and round spermatids formed were lower than in control cultures, despite similar cell viability. This effect of roscovitine was reversible, did not involve the Sertoli cells, and was dependent on the concentration of the inhibitor. Roscovitine did not modify the amount of MPF in these germ cells but inhibited the CDK1- or CDK2-associated histone H1 kinase activity of PS. Hence a functional relationship between cyclin-dependent kinase activity and the spontaneous processing of the first meiotic division and, for the first time, of the second meiotic division of male germ cells is shown.
Godet
Murielle
M
INSERM U418/INRA UMR 1245, Hôpital Debrousse, 69322 Lyon 05, France. godet@lyon.inserm.fr
Damestoy
Anne
A
Mouradian
Sandrine
S
Rudkin
Brian B
BB
Durand
Philippe
P
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism / Q000502:physiology*; D042846:CDC2-CDC28 Kinases / Q000378:metabolism / Q000502:physiology*; D048429:Cell Size; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D051357:Cyclin-Dependent Kinase 2; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D016200:Maturation-Promoting Factor / Q000378:metabolism; D008540:Meiosis / Q000502:physiology; D009994:Osmolar Concentration; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D000077546:Roscovitine; D012708:Sertoli Cells; D013087:Spermatids / Q000166:cytology / Q000502:physiology; D013090:Spermatocytes / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D011494:Protein Kinases; C102333:histone H1 kinase; D051360:Cyclin-Dependent Kinase 5; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; C495907:Cdk5 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016200:Maturation-Promoting Factor