NCBI Summary:
The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. This protein interacts with the recombination activating gene 1 (RAG1) protein and is a putative substrate of the RAG1 ubiquitin ligase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
General function
Comment
Cellular localization
Cytoplasmic, Nuclear
Comment
Ovarian function
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Expression regulated by
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Ovarian localization
Primordial Germ Cell, Oocyte
Comment
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.//////////////////
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Targeted disruption of one of the importin a family members leads to female functional incompetence in delivery. Moriyama T et al. Importin a mediates the nuclear import of proteins through nuclear pore complexes in eukaryotic cells and is common to all eukaryotes. Previous reports identified at least six importin a family genes in mice. Although these isoforms show differential binding to various import cargoes in vitro, the in vivo physiological roles of these mammalian importin a isoforms remain unknown. Here, we generated and examined importin a5 knockout (impa5(-/-) ) mice. Impa5(-/-) mice developed normally and showed no gross histological abnormalities in most major organs. However, the ovary and uterus of impa5(-/-) female mice exhibited hypoplasia. Furthermore, we found that impa5(-/-) female mice had a 50% decrease in the serum progesterone levels and a 57% decrease in the progesterone receptor (PR) mRNA levels in the ovary. Additionally, impa5(-/-) uteruses that were treated with exogenous gonadotropins displayed hypertrophy, similar to PR-deficient mice. Although these mutant female mice could become pregnant, the total number of pups was significantly decreased and some of the pups were dead at birth. These results suggest that importin a5 has essential roles in the mammalian female reproductive organs.