Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes.
In somatic cells, integrity of cell division is safeguarded by the spindle checkpoint, a signaling cascade that delays the separation of sister chromatids in the presence of misaligned chromosomes. Aurora kinases play important roles in this process by promoting centrosome maturation, chromosome bi-orientation, spindle checkpoint signaling, and cytokinesis. To investigate the functions of Aurora kinases in male meiosis, we applied a small molecule Aurora inhibitor, ZM447439, to seminiferous tubules in vitro. Primary and secondary spermatocytes exposed to ZM447439 exhibit defects in the spindle morphology and fail to align their chromosomes at the metaphase plate. Moreover, the treated spermatocytes undergo a forced exit from the meiotic M-phase without cytokinesis. These results suggest that the activities of Aurora kinases are required for normal spindle assembly as well as for establishment and maintenance of proper microtubule-kinetochore attachments and spindle checkpoint signaling in male mammalian meiosis.
Wang
Yangyang
Y
Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Toppari
Jorma
J
Parvinen
Martti
M
Kallio
Marko J
MJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D064127:Aurora Kinases; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology*; D048430:Cell Shape; D002478:Cells, Cultured; D002875:Chromosomes / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018816:Genes, cdc; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008540:Meiosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011799:Quinazolines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology*; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism*
C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D011799:Quinazolines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde