A5035101347- Nuclear Structure and Function
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- interferon and immune responses
- Cell death mechanisms and regulation
- Renal and related cancers
- Exercise and Physiological Responses
- Pluripotent Stem Cells Research
- Influenza Virus Research Studies
- Animal Disease Management and Epidemiology
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Hormonal Regulation and Hypertension
- Cellular Mechanics and Interactions
- Renin-Angiotensin System Studies
- Neuroendocrine regulation and behavior
- Toxin Mechanisms and Immunotoxins
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- Nerve injury and regeneration
- Herpesvirus Infections and Treatments
- Viral Infections and Immunology Research
- Pain Mechanisms and Treatments
Max Delbrück Center
2011-2024
University of Lübeck
2011-2024
Influenza A viruses are a threat to humans due their ability cross species barriers, as illustrated by the 2009 H1N1v pandemic and sporadic H5N1 transmissions. Interspecies transmission requires adaptation of viral polymerase importin-α, cellular protein that mediates transport into nucleus where transcription replication genome takes place. In this study, we analysed replication, host specificity pathogenicity avian mammalian influenza viruses, in importin-α-silenced cells...
How is neuropathic pain regulated in peripheral sensory neurons? Importins are key regulators of nucleocytoplasmic transport. In this study, we found that importin α3 (also known as karyopherin subunit alpha 4) can control responsiveness neurons mice. Importin knockout or neuron-specific knockdown mice reduced to diverse noxious stimuli and increased tolerance pain. α3-bound c-Fos α3-deficient were impaired nuclear import. Knockdown dominant-negative inhibition c-Jun silico screens...
Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore host transport factors to ensure specific import of viral components. While some cargoes bind directly certain factors, most recruit importin β1 via α. We identified α1 in a small targeted siRNA screen be important for herpes simplex virus (HSV-1) gene expression. Production infectious virions was delayed the absence α1, but not cells lacking α3 or α4. targeting incoming capsids, HSV-1 transcription...
Significance Ataxin-3 is the affected protein in neurodegenerative disorder spinocerebellar ataxia type 3 (SCA3). Nuclear ataxin-3 has been linked to disease progression and formation of aggregates. Our present findings implicate karyopherin alpha (KPNA3) vitro transport SCA3-related phenotypes Drosophila mouse models. We have demonstrated that altering proteins an effect on both pathogenic mechanisms (e.g., intracellular localization aggregates) key features toxicity such as anxiety, total...
Importin α is involved in the nuclear import of proteins. It also contributes to spindle assembly and membrane formation, however, underlying mechanisms are poorly understood. Here, we studied function importin α7 by gene targeting mice show that it essential for early embryonic development. Embryos lacking display a reduced ability first cleavage arrest completely at two-cell stage. We zygotic genome activation severely disturbed these embryos. Our findings indicate new member small group...
Importins mediate transport from synapse to soma and cytoplasm nucleus, suggesting that perturbation of importin-dependent pathways should have significant neuronal consequences. A behavioral screen on five importin α knockout lines revealed reduced expression α5 (KPNA1) in hippocampal neurons specifically decreases anxiety mice. Re-expression ventral hippocampus animals increased behaviors wild-type levels. Hippocampal lacking reveal changes presynaptic plasticity modified MeCP2-regulated...
The nuclear transport of proteins plays an important role in mediating the transition from egg to embryo and distinct karyopherins have been implicated this process. Here, we studied impact KPNA2 deficiency on preimplantation development mice. Loss results complete arrest at 2cell stage embryos exhibit inability activate their embryonic genome as well a severely disturbed translocation Nucleoplasmin 2. Our findings define new maternal effect gene.
The importin α:β complex is responsible for the nuclear import of proteins bearing classical localization signals. In mammals, several α subtypes are known to exist that suggested have individual functions. Importin 7 was shown play a crucial role in early embryonic development mice. Embryos from 7-depleted females stop at two-cell stage and show disturbed zygotic genome activation. As there evidence possess cargo specificities, we hypothesized binds unique set intracellular proteins. With...
Satellite cells are stem with an essential role in skeletal muscle repair. Precise regulation of gene expression is critical for proper satellite cell quiescence, proliferation, differentiation and self-renewal. Nuclear proteins required dependent on the nucleocytoplasmic transport machinery to access nucleus, however little known about nuclear cells. The best characterized import pathway classical which depends a localization signal (cNLS) cargo protein heterodimeric receptors, karyopherin...
Spermatogenesis is driven by an ordered series of events, which rely on trafficking specific proteins between nucleus and cytoplasm. The karyopherin α family mediates movement cargo when bound to β. Karyopherin genes have distinct expression patterns in mouse testis, implying they may unique roles during mammalian spermatogenesis. Here, we use a loss-of-function approach determine specifically the role Kpna6 spermatogenesis male fertility. We show that ablation mice leads infertility has...
ABSTRACT The nuclear transport of proteins is mediated by karyopherins and has been implicated to be crucial for germ cell embryonic development. Deletion distinct members the karyopherin alpha family shown cause male female infertility in mice. Using a genetrap approach, we established mice deficient KPNA2 (KPNA2 KO) investigated role this protein development fertility. Breeding KO leads healthy offsprings all cases albeit absence resulted reduction sperm number 60%. Analyses expression...
The nuclear transport of proteins is mediated by karyopherins and has been implicated to be crucial for germ cell embryonic development. Deletion distinct members the karyopherin alpha family shown cause male female infertility in mice. Using a genetrap approach, we established mice deficient KPNA2 (KPNA2 KO) investigated role this protein development fertility. Breeding KO leads healthy offsprings all cases albeit absence resulted reduction sperm number 60%. Analyses expression wild-type...
Acute intra-renal infusion of bradykinin increases diuresis and natriuresis via inhibition vasopressin activity. However, the consequences chronically increased in kidneys have not yet been studied. A new transgenic animal model producing an excess by proximal tubular cells (KapBK rats) was generated submitted to different salt containing diets analyze changes blood pressure other cardiovascular parameters, urine excretion, composition, as well levels expression renin-angiotensin system...
ABSTRACT The nuclear transport of proteins plays an important role in mediating the transition from egg to embryo and distinct karyopherins have been implicated this process. Here, we studied impact KPNA2 deficiency on preimplantation development mice. Loss results complete arrest at 2cell stage embryos exhibit inability activate their embryonic genome as well a severely disturbed translocation Nucleoplasmin 2. Our findings define new maternal effect gene.
Abstract Spermatogenesis is driven by an ordered series of events, which rely on trafficking specific proteins between nucleus and cytoplasm. The importin α family mediates movement cargo when bound to β. Importin genes have distinct expression patterns in mouse testis, implying they may unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach specifically determine the role α7 spermatogenesis male fertility. We show that ablation mice leads infertility has...