Normal brain development in importin-α5 deficient-mice

Shmidt, Tatjana; Hampich, Franziska; Ridders, Michael; Schultrich, Stefanie; Hans, Volkmar; Tenner, Katja; Vilianovich, Larissa; Qadri, Fatimunnisa; Alenina, Natalia; Hartmann, Enno; Köhler, M; Bäder, Michael

doi:10.1038/ncb1207-1337

Cited by 38 publications

(37 citation statements)

References 8 publications

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“…KPNA1-null mice develop normally, 81,82) but show hypoplasia in female reproductive organs such as the ovary and uterus with severely reduced serum progesterone levels and progesterone receptor mRNA levels. 81) Analysis of KPNA1 knockout mice further revealed that KPNA1 is important for muscle regeneration.…”

Section: Lessons From Studies Of Importin αmentioning

confidence: 99%

Importin α: functions as a nuclear transport factor and beyond

Oka

Yoneda

2018

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

101

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Nucleocytoplasmic transport is an essential process in eukaryotes. The molecular mechanisms underlying nuclear transport that involve the nuclear transport receptor, small GTPase Ran, and the nuclear pore complex are highly conserved from yeast to humans. On the other hand, it has become clear that the nuclear transport system diverged during evolution to achieve various physiological functions in multicellular eukaryotes. In this review, we first summarize the molecular mechanisms of nuclear transport and how these were elucidated. Then, we focus on the diverse functions of importin α, which acts not merely an import factor but also as a multi-functional protein contributing to a variety of cellular functions in higher eukaryotes.

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Section: Lessons From Studies Of Importin αmentioning

confidence: 99%

Importin α: functions as a nuclear transport factor and beyond

Oka

Yoneda

2018

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

101

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“…Likewise, importin-α isoform expression in spermatogenesis has been extensively studied, showing significant variations in expression levels of importin α1, in particular, throughout the process [58,60,61]. Any one of the importin α4, α5, α7 or α8 knockouts in mice did not lead to abnormal brain development [54,62–65], suggesting that the loss of a single isoform gene is probably compensated for in vivo by an isoform of the same subfamily. Instead, the importin α5 and α7 knockouts led to reproductive problems in female mice and the importin α8 knockout causes reduced fertility and sex imbalance in litters due to induced lethality in females [54], suggesting some non-redundant function of these isoforms in reproduction.…”

Section: Evolution and Diversification Of The Importin-α Gene In Eukamentioning

confidence: 99%

“…A mutation in human importin α8 has also been found to be associated with improper neuronal development [116]. However, the redundancy of the importin-α isoforms still allows for proper brain development even when one of these isoforms is lost, as seen when importin α5 was knocked down in mice [62]. …”

Section: Involvement Of Importin-α Isoforms In Human Diseasesmentioning

confidence: 99%

Diversification of importin-α isoforms in cellular trafficking and disease states

Pumroy

Cingolani

2015

Biochemical Journal

204

210

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The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases.

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“…In addition, mouse Cyclin D2 mutant B lymphocytes exhibit no obvious proliferative phenotype due to the upregulation of Cyclin D3 [61]. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of Importinα5 was reported to inhibit neural differentiation of mESCs cells [62]; however, Importinα5 mutant mice display normal brain development, possibly due to the upregulation of IMPORTINα4 expression [63]. siRNA-mediated knockdown of Kindlin-2 , which encodes an integrin coactivator, in mouse embryonic fibroblasts (MEFs) was reported to decrease INTEGRIN β1 activation and prevent INTERLEUKIN 1β–mediated increase in focal adhesion number [64].…”

Section: Introductionmentioning

confidence: 99%

Genetic compensation: A phenomenon in search of mechanisms

2017

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Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.

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Normal brain development in importin-α5 deficient-mice

Cited by 38 publications

References 8 publications

Importin α: functions as a nuclear transport factor and beyond

Importin α: functions as a nuclear transport factor and beyond

Diversification of importin-α isoforms in cellular trafficking and disease states

Genetic compensation: A phenomenon in search of mechanisms

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