Nuclear polarity and nuclear trafficking inDrosophila

1997 ◽  
Vol 8 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Ilan Davis
Keyword(s):  
Nuclear Trafficking ◽  
Nuclear Polarity

scholarly journals Aberrant Nuclear Trafficking of La Protein Leads to Disordered Processing of Associated Precursor tRNAs

2002 ◽  
Vol 9 (5) ◽  
pp. 1113-1123 ◽  
Author(s):  
Robert V Intine ◽  
Miroslav Dundr ◽  
Tom Misteli ◽  
Richard J Maraia
Keyword(s):  
Nuclear Trafficking ◽  
La Protein

scholarly journals Staufen1 is imported into the nucleolus via a bipartite nuclear localization signal and several modulatory determinants

2005 ◽  
Vol 393 (1) ◽  
pp. 245-254 ◽  
Author(s):  
Catherine Martel ◽  
Paolo Macchi ◽  
Luc Furic ◽  
Michael A. Kiebler ◽  
Luc Desgroseillers
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Nuclear Export ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Binding Activity ◽  
Nuclear Trafficking ◽  
Binding Domains ◽  
Bipartite Nuclear Localization Signal ◽  
Localization Signal

Mammalian Stau1 (Staufen1), a modular protein composed of several dsRBDs (double-stranded RNA-binding domains), is probably involved in mRNA localization. Although Stau1 is mostly described in association with the rough endoplasmic reticulum and ribosomes in the cytoplasm, recent studies suggest that it may transit through the nucleus/nucleolus. Using a sensitive yeast import assay, we show that Stau1 is actively imported into the nucleus through a newly identified bipartite nuclear localization signal. As in yeast, the bipartite nuclear localization signal is necessary for Stau1 nuclear import in mammalian cells. It is also required for Stau1 nucleolar trafficking. However, Stau1 nuclear transit seems to be regulated by mechanisms that involve cytoplasmic retention and/or facilitated nuclear export. Cytoplasmic retention is mainly achieved through the action of dsRBD3, with dsRBD2 playing a supporting role in this function. Similarly, dsRBD3, but not its RNA-binding activity, is critical for Stau1 nucleolar trafficking. The function of dsRBD3 is strengthened or stabilized by the presence of dsRBD4 but prevented by the interdomain between dsRBD2 and dsRBD3. Altogether, these results suggest that Stau1 nuclear trafficking is a highly regulated process involving several determinants. The presence of Stau1 in the nucleus/nucleolus suggests that it may be involved in ribonucleoprotein formation in the nucleus and/or in other nuclear functions not necessarily related to mRNA transport.

Molecular Basis for Dissimilar Nuclear Trafficking of the Actin-Bundling Protein Isoforms T- and L-Plastin

Traffic ◽  
2005 ◽  
Vol 6 (4) ◽  
pp. 335-345 ◽  
Author(s):  
Veerle Delanote ◽  
Katrien Van Impe ◽  
Veerle De Corte ◽  
Erik Bruyneel ◽  
Guillaume Vetter ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Protein Isoforms ◽  
Nuclear Trafficking

scholarly journals Mitotic antipairing of homologous and sex chromosomes via spatial restriction of two haploid sets

2018 ◽  
Vol 115 (52) ◽  
pp. E12235-E12244 ◽  
Author(s):  
Lisa L. Hua ◽  
Takashi Mikawa
Keyword(s):  
Genome Instability ◽  
Cell Types ◽  
Parental Origin ◽  
Meridional Plane ◽  
Homologous Chromosomes ◽  
Daughter Cells ◽  
Homologous Chromosome Pairing ◽  
Multiple Cell ◽  
Mouse Cells ◽  
Nuclear Polarity

Pairing homologous chromosomes is required for recombination. However, in nonmeiotic stages it can lead to detrimental consequences, such as allelic misregulation and genome instability, and is rare in human somatic cells. How mitotic recombination is prevented—and how genetic stability is maintained across daughter cells—is a fundamental, unanswered question. Here, we report that both human and mouse cells impede homologous chromosome pairing by keeping two haploid chromosome sets apart throughout mitosis. Four-dimensional analysis of chromosomes during cell division revealed that a haploid chromosome set resides on either side of a meridional plane, crossing two centrosomes. Simultaneous tracking of chromosome oscillation and the spindle axis, using fluorescent CENP-A and centrin1, respectively, demonstrates collective genome behavior/segregation of two haploid sets throughout mitosis. Using 3D chromosome imaging of a translocation mouse with a supernumerary chromosome, we found that this maternally derived chromosome is positioned by parental origin. These data, taken together, support the identity of haploid sets by parental origin. This haploid set-based antipairing motif is shared by multiple cell types, doubles in tetraploid cells, and is lost in a carcinoma cell line. The data support a mechanism of nuclear polarity that sequesters two haploid sets along a subcellular axis. This topological segregation of haploid sets revisits an old model/paradigm and provides implications for maintaining mitotic fidelity.

scholarly journals Microtubule- and Dynein-Dependent Nuclear Trafficking of Rhesus Rhadinovirus in Rhesus Fibroblasts

2011 ◽  
Vol 86 (1) ◽  
pp. 599-604 ◽  
Author(s):  
W. Zhang ◽  
W. Greene ◽  
S.-J. Gao
Keyword(s):  
Nuclear Trafficking

scholarly journals Genetic Evidence for a Connection between Rous Sarcoma Virus Gag Nuclear Trafficking and Genomic RNA Packaging

2009 ◽  
Vol 83 (13) ◽  
pp. 6790-6797 ◽  
Author(s):  
Rachel Garbitt-Hirst ◽  
Scott P. Kenney ◽  
Leslie J. Parent
Keyword(s):  
Nuclear Localization ◽  
Rous Sarcoma Virus ◽  
Rna Binding ◽  
Genetic Evidence ◽  
Genomic Rna ◽  
Wild Type ◽  
Nuclear Trafficking ◽  
Gag Protein ◽  
Rous Sarcoma ◽  
Sarcoma Virus

ABSTRACT The packaging of retroviral genomic RNA (gRNA) requires cis-acting elements within the RNA and trans-acting elements within the Gag polyprotein. The packaging signal ψ, at the 5′ end of the viral gRNA, binds to Gag through interactions with basic residues and Cys-His box RNA-binding motifs in the nucleocapsid. Although specific interactions between Gag and gRNA have been demonstrated previously, where and when they occur is not well understood. We discovered that the Rous sarcoma virus (RSV) Gag protein transiently localizes to the nucleus, although the roles of Gag nuclear trafficking in virus replication have not been fully elucidated. A mutant of RSV (Myr1E) with enhanced plasma membrane targeting of Gag fails to undergo nuclear trafficking and also incorporates reduced levels of gRNA into virus particles compared to those in wild-type particles. Based on these results, we hypothesized that Gag nuclear entry might facilitate gRNA packaging. To test this idea by using a gain-of-function genetic approach, a bipartite nuclear localization signal (NLS) derived from the nucleoplasmin protein was inserted into the Myr1E Gag sequence (generating mutant Myr1E.NLS) in an attempt to restore nuclear trafficking. Here, we report that the inserted NLS enhanced the nuclear localization of Myr1E.NLS Gag compared to that of Myr1E Gag. Also, the NLS sequence restored gRNA packaging to nearly wild-type levels in viruses containing Myr1E.NLS Gag, providing genetic evidence linking nuclear trafficking of the retroviral Gag protein with gRNA incorporation.

scholarly journals Emerging roles for nucleoporins in reproductive cellular physiology

2019 ◽  
Vol 97 (4) ◽  
pp. 257-264
Author(s):  
Claudia C. Preston ◽  
Emily C. Storm ◽  
Riley J. Leonard ◽  
Randolph S. Faustino
Keyword(s):  
Next Generation Sequencing ◽  
Nucleocytoplasmic Transport ◽  
Human Reproduction ◽  
Nuclear Pore ◽  
Next Generation ◽  
Nuclear Trafficking ◽  
Next Generation Sequencing Technology ◽  
Powerful Approach ◽  
Reproductive Disease ◽  
Generation Sequencing

Nucleoporins are a specialized subset of nuclear proteins that comprise the nuclear pore complex and regulate nucleocytoplasmic transport. Recent demonstrations of roles for individual nucleoporins in multiple paradigms of differentiation via mechanisms independent of nuclear trafficking represent conceptual advances in understanding the contributions of nucleoporins to cellular development. Among these, a functional role for nucleoporins in reproductive fitness and gametogenesis has been identified, supported by robust models and clinical studies that leverage the power of next generation sequencing technology to identify reproductive-disease-associated mutations in specific nucleoporins. Proper nucleoporin function manifests in different ways during oogenesis and spermatogenesis. However, nonhuman models of gametogenesis may not recapitulate human mechanisms, which may confound translational interpretation and relevance. To circumvent these limitations, identification of reproductive pathologies in patients, combined with next generation sequencing approaches and advanced in silico tools, offers a powerful approach to investigate the potential function of nucleoporins in human reproduction. Ultimately, elucidating the role of nucleoporins in reproductive biology will provide opportunities for predictive, diagnostic, and therapeutic strategies to address reproductive disorders.

scholarly journals Core Protein-Directed Antivirals and Importin β Can Synergistically Disrupt HBV Capsids

2021 ◽  
Author(s):  
Christine Kim ◽  
Lauren Barnes ◽  
Christopher Schlicksup ◽  
Angela Patterson ◽  
Brian Bothner ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Core Protein ◽  
Innate Immune ◽  
Host Protein ◽  
Structural Proteins ◽  
Nuclear Trafficking ◽  
Terminal Domain ◽  
Viral Lifecycle ◽  
Capsid Stability

ABSTRACTViral structural proteins can have multiple activities. Antivirals that target structural proteins have potential to exhibit multiple antiviral mechanisms. Hepatitis B Virus (HBV) core protein (Cp) is involved in most stages of the viral lifecycle: it assembles into capsids, packages viral RNA, is a metabolic compartment for reverse transcription, interacts with nuclear trafficking machinery, and disassembles to release the viral genome into the nucleus. During nuclear localization, HBV capsids bind to host importins (e.g. Impβ) via Cp’s C-terminal domain (CTD); the CTD is localized to the interior of the capsid and is transiently exposed on the exterior. We used HAP12 as a representative Cp Allosteric Modulators (CpAMs), a class of antivirals that inappropriately stimulates and misdirects HBV assembly and deforms capsids. CpAM impact on other aspects of the HBV lifecycle is poorly understood. We investigated how HAP12 influenced the interactions between empty or RNA-filled capsids with Impβ and trypsin in vitro. We showed that HAP12 can modulate CTD accessibility and capsid stability, depending on the saturation of HAP12-binding sites. We demonstrated that Impβ synergistically contributes to capsid disruption at high levels of HAP12 saturation, using electron microscopy to visualize disruption and rearrangement of Cp dimers into aberrant complexes. However, RNA-filled capsids resisted the destabilizing effects of HAP12 and Impβ. In summary, we show host protein-induced catalysis of capsid disruption, an unexpected additional mechanism of action for CpAMs. Potentially, untimely capsid disassembly can hamper the HBV lifecycle and also cause the virus to become vulnerable to host innate immune responses.IMPORTANCEThe HBV core, an icosahedral complex of 120 copies of the homodimeric core (capsid) protein with or without packaged nucleic acid, is transported to the host nucleus by its interaction with host importin proteins. Importin-core interaction requires the core protein C-terminal domain, which is inside the capsid, to “flip” to the capsid exterior. Core-protein directed drugs that affect capsid assembly and stability have been developed recently. We show that these molecules can, synergistically with importins, disrupt capsids. This mechanism of action, synergism with host protein, has potential to disrupt the virus lifecycle and activate the innate immune system.

scholarly journals Phenotypic Divergence of P Proteins of Australian Bat Lyssavirus Lineages Circulating in Microbats and Flying Foxes

2021 ◽  
Author(s):  
Celine Deffrasnes ◽  
Meng-Xiao Luo ◽  
Linda Wiltzer ◽  
Cassandra T David ◽  
Kim G Lieu ◽  
...  
Keyword(s):  
Molecular Mapping ◽  
Protein A ◽  
Fine Tuning ◽  
Nuclear Trafficking ◽  
P Protein ◽  
Phenotypic Divergence ◽  
Reservoir Species ◽  
Pathogenic Viruses ◽  
P Proteins ◽  
Australian Bat Lyssavirus

Bats are reservoirs of many pathogenic viruses including the lyssaviruses rabies virus (RABV) and Australian bat lyssavirus (ABLV). Lyssavirus strains are closely associated with particular host reservoir species, with evidence of specific adaptation. Associated phenotypic changes remain poorly understood but are likely to involve P protein, a key mediator of the intracellular virus-host interface. Here, we examine the phenotype of P protein of ABLV, which circulates as two defined lineages associated with frugivorous and insectivorous bats, providing the opportunity compare proteins of viruses adapted to divergent bat species. We report that key functions of P protein in interferon/STAT1 antagonism and the capacity of P protein to undergo nuclear trafficking differ between lineages. Molecular mapping indicates that these differences are functionally distinct, and appear to involve modulatory effects on regulatory regions or structural impact, rather than changes to defined interaction sequences. This results in partial but significant phenotypic divergence, consistent with ‘fine-tuning’ to host biology, and with potentially distinct properties in the virus-host interface between bat families that represent key zoonotic reservoirs.

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