Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes.

• Main Authors: Stéphane Brunet, Julien Dumont, Karen W Lee, Kazuhisa Kinoshita, Pascale Hikal, Oliver J Gruss, Bernard Maro, Marie-Hélène Verlhac
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2008-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2556383?pdf=render

Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself.