Aurora-A is involved in resumption of meiosis and spindle formation in mouse oocytes

0089296 - ÚŽFG 2008 RIV DE eng K - Konferenční příspěvek (tuzemská konf.)
Šašková, Adéla - Šolc, Petr - Baran, V. - Kubelka, Michal - Motlík, Jan
Aurora-A is involved in resumption of meiosis and spindle formation in mouse oocytes.
[Aurora-A je zhrnuta v znovuzahájení meiosy a formaci metafáze I spindlu.]
Horizons in Molecular Biology International PhD Student Symposium and Career Fair for Scientists /4./. Göttingen: -, 2007, s. 71-71.
[Horizons in Molecular Biology International PhD Student Symposium and Career Fair for Scientists /4./. Göttingen (DE), 12.09.2007-15.09.2007]
Výzkumný záměr: CEZ:AV0Z50450515
Klíčová slova: meiosis
Kód oboru RIV: EB - Genetika a molekulární biologie

We study the role of Aurora-A during meiotic maturation of mouse oocytes. Total Aurora-A is present in the nucleus in GV-stage oocytes (G2 equivalent). Additionally, active Aurora-A is localized entirely to the centrosome (MTOC) shorly before germinal vesicle breakdown (GVBD). Compared to somatic cells, where active Aurora-A is at the centrosomes and the spindle poles, active Aurora-A is strictly localized on MTOCs at metaphase I in oocytes. We show that activation of centrosomal Aurora-A is independent on PI3K-PKB and CDK1 signaling pathways. This was proved by cultivation of oocytes in presence of roscovitine (CDK1 inhibitor), LY-294002 (PI3K inhibitor) and SH-6 (PKB inhibitor). Treated oocytes show high phosphorylation of Aurora-A on T288 and centrosome amplification despite the presence of intact nuclear envelope. Silencing of Aurora-A by RNA interference induces incorrect spindle assembly. Oocytes are arrested in prometaphase I and unable to reach metaphase II. After microinjection of eGFP-Aurora-A mRNA into GV-stage oocytes, overexpression of Aurora-A leads to distortion of MI spindle organization as well. Our results indicate that Aurora-A is the key centrosomal player in meiotic maturation, essential for proper spindle formation and metaphase I - metaphase II transition.

Práce se zabývá úlohou Aurora-A kinázy během meiotického zrání in vitro. Pomocí farmakologické inhibice PI3K, PKB a CDK1 bylo prokázáno, že Aurora-A, se aktivuje velmi časně při znovuzahájení meiosy, a toto aktivace je nezávislá na PI3K-PKB a CDK1 signalizaci. Dále bylo prokázáno (RNA interference, mikroinjekce mRNA), že Aurora-A je nutná pro korektní výstavbu metafáze I spindelu a pro metafase I – metafase II přechod.
Trvalý link: http://hdl.handle.net/11104/0150551