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Changing expression and subcellular distribution of karyopherins during murine oogenesis. Mihalas B et al. (2015) Mammalian oocyte growth and development is driven by a strict program of gene expression that relies on the timely presence of transcriptional regulators via nuclear pores. By targeting specific cargos for nucleo-cytoplasmic transport, karyopherin proteins are key to the relocation of essential transcription factors and chromatin-remodeling factors into and out of the nucleus. Using multiple complementary techniques, here we establish that karyopherin genes and proteins are dynamically expressed and relocalised throughout mouse oogenesis and folliculogenesis. Of the karyopherins examined (Kpna1, Kpna2, Kpna3, Kpna4, Kpna6, Kpna7, Kpnb1, Ipo5 and Xpo1), all were expressed in the embryonic ovary with up-regulation of protein levels concomitant with meiotic entry for KPNA2, accompanied by redistribution of cellular localisation of KPNA2 and XPO1. In contrast, postnatal folliculogenesis revealed significant up-regulation of Kpna1, Kpna2, Kpna4, Kpna6 and Ipo5 and down-regulation of Kpnb1, Kpna7 and Xpo1 at the primordial to primary follicle transition. Karyopherins exhibited different localisation patterns in both oocytes and granulosa cells during folliculogenesis, with three karyopherins KPNA1, KPNA2 and IPO5, displaying marked enrichment in the nucleus by antral follicle stage. Remarkably varied subcellular expression profiles were also identified in isolated pre-ovulatory oocytes with karyopherins KPNA2, KPNB1 and IPO5 detected in the cytoplasm and at the nuclear rim and XPO1 in cytoplasmic aggregates. Intriguingly meiotic spindle staining was also observed for KPNB1 and XPO1 in MII eggs, implying roles for karyopherins outside of nucleo-cytoplasmic transport. Thus we propose that karyopherins, by targeting specific cargoes are likely to be key regulators of oocyte development.//////////////////
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