Publications by authors named "Victoria Shabardina"

10 Publications

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Tracing the evolutionary history of Ca-signaling modulation by human Bcl-2: Insights from the Capsaspora owczarzaki IP receptor ortholog.

Biochim Biophys Acta Mol Cell Res 2021 Aug 14;1868(12):119121. Epub 2021 Aug 14.

KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, and Leuven Kanker Instituut, 3000 Leuven, Belgium. Electronic address:

Recently, a functional IPR ortholog (CO.IPR-A) capable of IP-induced Ca release has been discovered in Capsaspora owczarzaki, a close unicellular relative to Metazoa. In contrast to mammalian IPRs, CO.IPR-A is not modulated by Ca, ATP or PKA. Protein-sequence analysis revealed that CO.IPR-A contained a putative binding site for anti-apoptotic Bcl-2, although Bcl-2 was not detected in Capsaspora owczarzaki and only appeared in Metazoa. Here, we examined whether human Bcl-2 could form a complex with CO.IPR-A channels and modulate their Ca-flux properties using ectopic expression approaches in a HEK293 cell model in which all three IPR isoforms were knocked out. We demonstrate that human Bcl-2 via its BH4 domain could functionally interact with CO.IPR-A, thereby suppressing Ca flux through CO.IPR-A channels. The BH4 domain of Bcl-2 was sufficient for interaction with CO.IPR-A channels. Moreover, mutating the Lys17 of Bcl-2's BH4 domain, the residue critical for Bcl-2-dependent modulation of mammalian IPRs, abrogated Bcl-2's ability to bind and inhibit CO.IPR-A channels. Hence, this raises the possibility that a unicellular ancestor of animals already had an IPR that harbored a Bcl-2-binding site. Bcl-2 proteins may have evolved as controllers of IPR function by exploiting this pre-existing site, thereby counteracting Ca-dependent apoptosis.
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http://dx.doi.org/10.1016/j.bbamcr.2021.119121DOI Listing
August 2021

Stable transfection in protist Corallochytriumlimacisporum identifies novel cellular features among unicellular animals relatives.

Curr Biol 2021 Jul 14. Epub 2021 Jul 14.

Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Passeig Marítim de la Barceloneta 37-49, 08003 Barcelona, Catalonia, Spain. Electronic address:

The evolutionary path from protists to multicellular animals remains a mystery. Recent work on the genomes of several unicellular relatives of animals has shaped our understanding of the genetic changes that may have occurred in this transition. However, the specific cellular modifications that took place to accommodate these changes remain unclear. To address this, we need to compare metazoan cells with those of their extant relatives, which are choanoflagellates, filastereans, ichthyosporeans, and corallochytreans/pluriformeans. Interestingly, these lineages display a range of developmental patterns potentially homologous to animal ones. Genetic tools have already been established in three of those lineages. However, there are no genetic tools available for Corallochytrea. We here report the development of stable transfection in the corallochytrean Corallochytrium limacisporum. Using these tools, we discern previously unknown biological features of C. limacisporum. In particular, we identify two different paths for cell division-binary fission and coenocytic growth-that reveal a non-linear life cycle. Additionally, we found that C. limacisporum is binucleate for most of its life cycle, and that, contrary to what happens in most eukaryotes, nuclear division is decoupled from cellular division. Moreover, its actin cytoskeleton shares characteristics with both fungal and animal cells. The establishment of these tools in C. limacisporum fills an important gap in the unicellular relatives of animals, opening up new avenues of research to elucidate the specific cellular changes that occurred in the evolution of animals.
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http://dx.doi.org/10.1016/j.cub.2021.06.061DOI Listing
July 2021

Somatic Functional Deletions of Upstream Open Reading Frame-Associated Initiation and Termination Codons in Human Cancer.

Biomedicines 2021 May 29;9(6). Epub 2021 May 29.

Department of Medicine A, Hematology, Oncology, Hemostaseology and Pneumology, University Hospital Münster, 48149 Münster, Germany.

Upstream open reading frame (uORF)-mediated translational control has emerged as an important regulatory mechanism in human health and disease. However, a systematic search for cancer-associated somatic uORF mutations has not been performed. Here, we analyzed the genetic variability at canonical (uAUG) and alternative translational initiation sites (aTISs), as well as the associated upstream termination codons (uStops) in 3394 whole-exome-sequencing datasets from patient samples of breast, colon, lung, prostate, and skin cancer and of acute myeloid leukemia, provided by The Cancer Genome Atlas research network. We found that 66.5% of patient samples were affected by at least one of 5277 recurrent uORF-associated somatic single nucleotide variants altering 446 uAUG, 347 uStop, and 4733 aTIS codons. While twelve uORF variants were detected in all entities, 17 variants occurred in all five types of solid cancer analyzed here. Highest frequencies of individual somatic variants in the TLSs of NBPF20 and CHCHD2 reached 10.1% among LAML and 8.1% among skin cancer patients, respectively. Functional evaluation by dual luciferase reporter assays identified 19 uORF variants causing significant translational deregulation of the associated main coding sequence, ranging from 1.73-fold induction for an AUG.1 > UUG variant in SETD4 to 0.006-fold repression for a CUG.6 > GUG variant in HLA-DRB1. These data suggest that somatic uORF mutations are highly prevalent in human malignancies and that defective translational regulation of protein expression may contribute to the onset or progression of cancer.
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http://dx.doi.org/10.3390/biomedicines9060618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227997PMC
May 2021

Genome assembly and annotation of the California harvester ant Pogonomyrmex californicus.

G3 (Bethesda) 2021 01;11(1)

Faculty of Medicine, Institute of Bioinformatics, University of Münster, 48149 Münster, Germany.

The harvester ant genus Pogonomyrmex is endemic to arid and semiarid habitats and deserts of North and South America. The California harvester ant Pogonomyrmex californicus is the most widely distributed Pogonomyrmex species in North America. Pogonomyrmex californicus colonies are usually monogynous, i.e. a colony has one queen. However, in a few populations in California, primary polygyny evolved, i.e. several queens cooperate in colony founding after their mating flights and continue to coexist in mature colonies. Here, we present a genome assembly and annotation of P. californicus. The size of the assembly is 241 Mb, which is in agreement with the previously estimated genome size. We were able to annotate 17,889 genes in total, including 15,688 protein-coding ones with BUSCO (Benchmarking Universal Single-Copy Orthologs) completeness at a 95% level. The presented P. californicus genome assembly will pave the way for investigations of the genomic underpinnings of social polymorphism in the number of queens, regulation of aggression, and the evolution of adaptations to dry habitats.
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http://dx.doi.org/10.1093/g3journal/jkaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022709PMC
January 2021

Emergence and Evolution of ERM Proteins and Merlin in Metazoans.

Genome Biol Evol 2020 01;12(1):3710-3724

Institue of Bioinformatics, University of Muenster, Germany.

Ezrin, radixin, moesin, and merlin are cytoskeletal proteins, whose functions are specific to metazoans. They participate in cell cortex rearrangement, including cell-cell contact formation, and play an important role in cancer progression. Here, we have performed a comprehensive phylogenetic analysis of the proteins spanning 87 species. The results describe a possible mechanism for the protein family origin in the root of Metazoa, paralogs diversification in vertebrates, and acquisition of novel functions, including tumor suppression. In addition, a merlin paralog, present in most vertebrates but lost in mammals, has been described here for the first time. We have also highlighted a set of amino acid variations within the conserved motifs as the candidates for determining physiological differences between ERM paralogs.
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http://dx.doi.org/10.1093/gbe/evz265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978628PMC
January 2020

Bioinformatics of nanopore sequencing.

J Hum Genet 2020 Jan 26;65(1):61-67. Epub 2019 Aug 26.

Institute of Bioinformatics, Faculty of Medicine, University of Münster, 48149, Münster, Germany.

Nanopore sequencing is one of the most exciting new technologies that undergo dynamic development. With its development, a growing number of analytical tools are becoming available for researchers. To help them better navigate this ever changing field, we discuss a range of software available to analyze sequences obtained using nanopore technology.
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http://dx.doi.org/10.1038/s10038-019-0659-4DOI Listing
January 2020

NanoPipe-a web server for nanopore MinION sequencing data analysis.

Gigascience 2019 02;8(2)

Institue of Bioinformatics, University of Muenster, Niels-Stensen-Strasse 14, Muenster, 48149, Germany.

Background: The fast-moving progress of the third-generation long-read sequencing technologies will soon bring the biological and medical sciences to a new era of research. Altogether, the technique and experimental procedures are becoming more straightforward and available to biologists from diverse fields, even without any profound experience in DNA sequencing. Thus, the introduction of the MinION device by Oxford Nanopore Technologies promises to "bring sequencing technology to the masses" and also allows quick and operative analysis in field studies. However, the convenience of this sequencing technology dramatically contrasts with the available analysis tools, which may significantly reduce enthusiasm of a "regular" user. To really bring the sequencing technology to every biologist, we need a set of user-friendly tools that can perform a powerful analysis in an automatic manner.

Findings: NanoPipe was developed in consideration of the specifics of the MinION sequencing technologies, providing accordingly adjusted alignment parameters. The range of the target species/sequences for the alignment is not limited, and the descriptive usage page of NanoPipe helps a user to succeed with NanoPipe analysis. The results contain alignment statistics, consensus sequence, polymorphisms data, and visualization of the alignment. Several test cases are used to demonstrate the efficiency of the tool.

Conclusions: Freely available NanoPipe software allows effortless and reliable analysis of MinION sequencing data for experienced bioinformaticians, as well for wet-lab biologists with minimum bioinformatics knowledge. Moreover, for the latter group, we describe the basic algorithm necessary for MinION sequencing analysis from the first to last step.
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http://dx.doi.org/10.1093/gigascience/giy169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377397PMC
February 2019

Environmental adaptation of and at genome level as seen by comparative genomic analysis.

Int J Biol Sci 2018 12;14(3):306-320. Epub 2018 Feb 12.

Institute of Bioinformatics, University Münster, Niels-Stensen Strasse 14, Münster 48149, Germany.

Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of . Nevertheless, both species prosper, demonstrating fitness to their specific environments. Here we compare transcriptomes of and with application of orthologs' search and gene ontology to learn how different life strategies influence genome evolution and restructuring of physiology demonstrates great metabolic activity and plasticity, while reveals several interesting features in its translational machinery, cytoskeleton, antioxidant protection, and nutritional behavior. In addition, we suggest new features in physiology that may explain its successful colonization of human colon and may facilitate medical research.
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http://dx.doi.org/10.7150/ijbs.23869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859476PMC
April 2019

The emerging picture of the mitochondrial protein import complexes of Amoebozoa supergroup.

BMC Genomics 2017 12 29;18(1):997. Epub 2017 Dec 29.

Laboratory of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, 61-614, Poznan, Poland.

Background: The existence of mitochondria-related organelles (MROs) is proposed for eukaryotic organisms. The Amoebozoa includes some organisms that are known to have mitosomes but also organisms that have aerobic mitochondria. However, the mitochondrial protein apparatus of this supergroup remains largely unsampled, except for the mitochondrial outer membrane import complexes studied recently. Therefore, in this study we investigated the mitochondrial inner membrane and intermembrane space complexes, using the available genome and transcriptome sequences.

Results: When compared with the canonical cognate complexes described for the yeast Saccharomyces cerevisiae, amoebozoans with aerobic mitochondria, display lower differences in the number of subunits predicted for these complexes than the mitochondrial outer membrane complexes, although the predicted subunits appear to display different levels of diversity in regard to phylogenetic position and isoform numbers. For the putative mitosome-bearing amoebozoans, the number of predicted subunits suggests the complex elimination distinctly more pronounced than in the case of the outer membrane ones.

Conclusion: The results concern the problem of mitochondrial and mitosome protein import machinery structural variability and the reduction of their complexity within the currently defined supergroup of Amoebozoa. This results are crucial for better understanding of the Amoebozoa taxa of both biomedical and evolutionary importance.
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http://dx.doi.org/10.1186/s12864-017-4383-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747110PMC
December 2017

Mode of Ezrin-Membrane Interaction as a Function of PIP2 Binding and Pseudophosphorylation.

Biophys J 2016 Jun;110(12):2710-2719

Institute of Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany; Göttingen Center for Molecular Biosciences, Göttingen, Germany. Electronic address:

Ezrin, a protein of the ezrin, radixin, moesin (ERM) family, provides a regulated linkage between the plasma membrane and the cytoskeleton. The hallmark of this linkage is the activation of ezrin by phosphatidylinositol-4,5-bisphosphate (PIP2) binding and a threonine phosphorylation at position 567. To analyze the influence of these activating factors on the organization of ezrin on lipid membranes and the proposed concomitant oligomer-monomer transition, we made use of supported lipid bilayers in conjunction with atomic force microscopy and fluorescence microscopy. Bilayers doped with either PIP2 as the natural receptor lipid of ezrin or a Ni-nitrilotriacetic acid-equipped lipid to bind the proteins via their His6-tags to the lipid membrane were used to bind two different ezrin variants: ezrin wild-type and ezrin T567D mimicking the phosphorylated state. Using a combination of reflectometric interference spectroscopy, atomic force microscopy, and Förster resonance energy transfer experiments, we show that only the ezrin T567D mutant, upon binding to PIP2-containing bilayers, undergoes a remarkable conformational change, which we attribute to an opening of the conformation resulting in monomeric protein on the lipid bilayer.
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http://dx.doi.org/10.1016/j.bpj.2016.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919509PMC
June 2016
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