Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes

Yangyang Wang, Jorma Toppari, Martti Parvinen, Marko Kallio (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)3459-3470
JournalExperimental Cell Research
Volume312
Issue number18
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fingerprint

Aurora Kinases
Spermatocytes
Meiosis
Cytokinesis
Chromosomes
Centrosome
Seminiferous Tubules
Chromatids
Metaphase
Cell Division
Maintenance
4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline

Keywords

  • Aurora kinases
  • Meiosis
  • Spindle checkpoint
  • ZM447439

Cite this

Wang, Yangyang ; Toppari, Jorma ; Parvinen, Martti ; Kallio, Marko. / Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes. In: Experimental Cell Research. 2006 ; Vol. 312, No. 18. pp. 3459-3470.
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Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes. / Wang, Yangyang; Toppari, Jorma; Parvinen, Martti; Kallio, Marko (Corresponding Author).

In: Experimental Cell Research, Vol. 312, No. 18, 2006, p. 3459-3470.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes

AU - Wang, Yangyang

AU - Toppari, Jorma

AU - Parvinen, Martti

AU - Kallio, Marko

PY - 2006

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N2 - 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.

AB - 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.

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KW - Spindle checkpoint

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