[{"publication":"Cell","external_id":{"isi":["000408372400014"]},"title":"DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","creator":"dernst","date_updated":"2020-07-14T12:48:08Z","file_id":"5852","date_created":"2019-01-18T13:45:40Z","checksum":"64897b0c5373f22273f598e4672c60ff","file_size":17666637,"file_name":"2017_Cell_Samwer.pdf"}],"citation":{"mla":"Samwer, Matthias, et al. “DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes.” <i>Cell</i>, vol. 170, no. 5, Cell Press, 2017, pp. 956–72, doi:<a href=\"https://doi.org/10.1016/j.cell.2017.07.038\">10.1016/j.cell.2017.07.038</a>.","short":"M. Samwer, M. Schneider, R. Hoefler, P.S. Schmalhorst, J. Jude, J. Zuber, D. Gerlic, Cell 170 (2017) 956–972.","ista":"Samwer M, Schneider M, Hoefler R, Schmalhorst PS, Jude J, Zuber J, Gerlic D. 2017. DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. Cell. 170(5), 956–972.","apa":"Samwer, M., Schneider, M., Hoefler, R., Schmalhorst, P. S., Jude, J., Zuber, J., &#38; Gerlic, D. (2017). DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2017.07.038\">https://doi.org/10.1016/j.cell.2017.07.038</a>","ama":"Samwer M, Schneider M, Hoefler R, et al. DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. <i>Cell</i>. 2017;170(5):956-972. doi:<a href=\"https://doi.org/10.1016/j.cell.2017.07.038\">10.1016/j.cell.2017.07.038</a>","chicago":"Samwer, Matthias, Maximilian Schneider, Rudolf Hoefler, Philipp S Schmalhorst, Julian Jude, Johannes Zuber, and Daniel Gerlic. “DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes.” <i>Cell</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cell.2017.07.038\">https://doi.org/10.1016/j.cell.2017.07.038</a>.","ieee":"M. Samwer <i>et al.</i>, “DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes,” <i>Cell</i>, vol. 170, no. 5. Cell Press, pp. 956–972, 2017."},"issue":"5","scopus_import":"1","has_accepted_license":"1","publication_status":"published","oa_version":"Published Version","page":"956 - 972","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"day":"24","abstract":[{"text":"Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF?s association with inner nuclear membrane proteins but instead relies on BAF?s ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function.","lang":"eng"}],"date_updated":"2023-09-27T10:59:14Z","acknowledged_ssus":[{"_id":"Bio"}],"status":"public","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","month":"08","quality_controlled":"1","publication_identifier":{"issn":["00928674"]},"publist_id":"6848","isi":1,"volume":170,"date_created":"2018-12-11T11:48:35Z","department":[{"_id":"CaHe"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","ddc":["570"],"file_date_updated":"2020-07-14T12:48:08Z","intvolume":"       170","author":[{"last_name":"Samwer","first_name":"Matthias","full_name":"Samwer, Matthias"},{"first_name":"Maximilian","full_name":"Schneider, Maximilian","last_name":"Schneider"},{"full_name":"Hoefler, Rudolf","first_name":"Rudolf","last_name":"Hoefler"},{"first_name":"Philipp S","full_name":"Schmalhorst, Philipp S","orcid":"0000-0002-5795-0133","id":"309D50DA-F248-11E8-B48F-1D18A9856A87","last_name":"Schmalhorst"},{"first_name":"Julian","full_name":"Jude, Julian","last_name":"Jude"},{"first_name":"Johannes","full_name":"Zuber, Johannes","last_name":"Zuber"},{"last_name":"Gerlic","first_name":"Daniel","full_name":"Gerlic, Daniel"}],"oa":1,"_id":"803","date_published":"2017-08-24T00:00:00Z","language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2017.07.038","publisher":"Cell Press","year":"2017","type":"journal_article"},{"acknowledged_ssus":[{"_id":"ScienComp"}],"status":"public","date_updated":"2023-09-27T10:58:45Z","abstract":[{"lang":"eng","text":"Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides."}],"page":"5039 - 5053","publication_status":"published","oa_version":"Submitted Version","day":"10","issue":"10","scopus_import":"1","citation":{"ama":"Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. <i>Journal of Chemical Theory and Computation</i>. 2017;13(10):5039-5053. doi:<a href=\"https://doi.org/10.1021/acs.jctc.7b00374\">10.1021/acs.jctc.7b00374</a>","apa":"Schmalhorst, P. S., Deluweit, F., Scherrers, R., Heisenberg, C.-P. J., &#38; Sikora, M. K. (2017). Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. <i>Journal of Chemical Theory and Computation</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acs.jctc.7b00374\">https://doi.org/10.1021/acs.jctc.7b00374</a>","mla":"Schmalhorst, Philipp S., et al. “Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides.” <i>Journal of Chemical Theory and Computation</i>, vol. 13, no. 10, American Chemical Society, 2017, pp. 5039–53, doi:<a href=\"https://doi.org/10.1021/acs.jctc.7b00374\">10.1021/acs.jctc.7b00374</a>.","short":"P.S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P.J. Heisenberg, M.K. Sikora, Journal of Chemical Theory and Computation 13 (2017) 5039–5053.","ista":"Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. 2017. Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. 13(10), 5039–5053.","ieee":"P. S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P. J. Heisenberg, and M. K. Sikora, “Overcoming the limitations of the MARTINI force field in simulations of polysaccharides,” <i>Journal of Chemical Theory and Computation</i>, vol. 13, no. 10. American Chemical Society, pp. 5039–5053, 2017.","chicago":"Schmalhorst, Philipp S, Felix Deluweit, Roger Scherrers, Carl-Philipp J Heisenberg, and Mateusz K Sikora. “Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides.” <i>Journal of Chemical Theory and Computation</i>. American Chemical Society, 2017. <a href=\"https://doi.org/10.1021/acs.jctc.7b00374\">https://doi.org/10.1021/acs.jctc.7b00374</a>."},"external_id":{"isi":["000412965700036"]},"title":"Overcoming the limitations of the MARTINI force field in simulations of polysaccharides","publication":"Journal of Chemical Theory and Computation","main_file_link":[{"url":"https://arxiv.org/abs/1704.03773","open_access":"1"}],"type":"journal_article","publisher":"American Chemical Society","year":"2017","language":[{"iso":"eng"}],"doi":"10.1021/acs.jctc.7b00374","date_published":"2017-10-10T00:00:00Z","oa":1,"_id":"804","author":[{"first_name":"Philipp S","full_name":"Schmalhorst, Philipp S","orcid":"0000-0002-5795-0133","last_name":"Schmalhorst","id":"309D50DA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Deluweit","full_name":"Deluweit, Felix","first_name":"Felix"},{"last_name":"Scherrers","first_name":"Roger","full_name":"Scherrers, Roger"},{"full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"},{"full_name":"Sikora, Mateusz K","first_name":"Mateusz K","last_name":"Sikora","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"}],"intvolume":"        13","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","department":[{"_id":"CaHe"}],"acknowledgement":"P.S.S. was supported by research fellowship 2811/1-1 from the German Research Foundation (DFG), and M.S. was supported by EMBO Long Term Fellowship ALTF 187-2013 and Grant GC65-32 from the  Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), University of Warsaw, Poland. The authors thank Antje Potthast, Marek Cieplak, Tomasz Włodarski, and Damien Thompson for fruitful discussions and the IST Austria Scientific Computing Facility for support.","date_created":"2018-12-11T11:48:35Z","volume":13,"isi":1,"quality_controlled":"1","publication_identifier":{"issn":["15499618"]},"publist_id":"6847","month":"10"},{"year":"2015","date_updated":"2021-01-12T08:16:33Z","publisher":"Oxford University Press","doi":"10.1093/glycob/cwv059","language":[{"iso":"eng"}],"type":"journal_article","status":"public","_id":"802","author":[{"last_name":"Engel","full_name":"Engel, Jakob","first_name":"Jakob"},{"orcid":"0000-0002-5795-0133","id":"309D50DA-F248-11E8-B48F-1D18A9856A87","last_name":"Schmalhorst","first_name":"Philipp S","full_name":"Schmalhorst, Philipp S"},{"last_name":"Kruger","first_name":"Anke","full_name":"Kruger, Anke"},{"first_name":"Christina","full_name":"Muller, Christina","last_name":"Muller"},{"first_name":"Falk","full_name":"Buettner, Falk","last_name":"Buettner"},{"first_name":"Françoise","full_name":"Routier, Françoise","last_name":"Routier"}],"abstract":[{"text":"Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man) linked at position 2 of the inositol. However, several pathogenic fungi additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC synthesized by this fungus. In this study, we identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC; a phenotype that could be reverted by episomal expression of GntA in the mutant. The N-acetylhexosaminyltransferase activity of GntA was substantiated by production of N-acetylhexosamine-IPC in the yeast Saccharomyces cerevisiae upon GntA expression. Using an in vitro assay, GntA was furthermore shown to use UDP-N-acetylglucosamine as donor substrate to generate a glycolipid product resistant to saponification and to digestion by phosphatidylinositol-phospholipase C as expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis.","lang":"eng"}],"day":"01","publication_status":"published","date_published":"2015-12-01T00:00:00Z","page":"1423 - 1430","oa_version":"None","department":[{"_id":"CaHe"}],"citation":{"chicago":"Engel, Jakob, Philipp S Schmalhorst, Anke Kruger, Christina Muller, Falk Buettner, and Françoise Routier. “Characterization of an N-Acetylglucosaminyltransferase Involved in Aspergillus Fumigatus Zwitterionic Glycoinositolphosphoceramide Biosynthesis.” <i>Glycobiology</i>. Oxford University Press, 2015. <a href=\"https://doi.org/10.1093/glycob/cwv059\">https://doi.org/10.1093/glycob/cwv059</a>.","ieee":"J. Engel, P. S. Schmalhorst, A. Kruger, C. Muller, F. Buettner, and F. Routier, “Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis,” <i>Glycobiology</i>, vol. 25, no. 12. Oxford University Press, pp. 1423–1430, 2015.","apa":"Engel, J., Schmalhorst, P. S., Kruger, A., Muller, C., Buettner, F., &#38; Routier, F. (2015). Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. <i>Glycobiology</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/glycob/cwv059\">https://doi.org/10.1093/glycob/cwv059</a>","mla":"Engel, Jakob, et al. “Characterization of an N-Acetylglucosaminyltransferase Involved in Aspergillus Fumigatus Zwitterionic Glycoinositolphosphoceramide Biosynthesis.” <i>Glycobiology</i>, vol. 25, no. 12, Oxford University Press, 2015, pp. 1423–30, doi:<a href=\"https://doi.org/10.1093/glycob/cwv059\">10.1093/glycob/cwv059</a>.","short":"J. Engel, P.S. Schmalhorst, A. Kruger, C. Muller, F. Buettner, F. Routier, Glycobiology 25 (2015) 1423–1430.","ista":"Engel J, Schmalhorst PS, Kruger A, Muller C, Buettner F, Routier F. 2015. Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. Glycobiology. 25(12), 1423–1430.","ama":"Engel J, Schmalhorst PS, Kruger A, Muller C, Buettner F, Routier F. Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. <i>Glycobiology</i>. 2015;25(12):1423-1430. doi:<a href=\"https://doi.org/10.1093/glycob/cwv059\">10.1093/glycob/cwv059</a>"},"pmid":1,"date_created":"2018-12-11T11:48:35Z","intvolume":"        25","scopus_import":1,"issue":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publist_id":"6851","quality_controlled":"1","month":"12","title":"Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis","external_id":{"pmid":["26306635"]},"volume":25,"publication":"Glycobiology"},{"publisher":"American Society for Biochemistry and Molecular Biology","year":"2012","language":[{"iso":"eng"}],"doi":"10.1074/jbc.M112.398321","type":"journal_article","_id":"801","author":[{"last_name":"Engel","first_name":"Jakob","full_name":"Engel, Jakob"},{"first_name":"Philipp S","full_name":"Schmalhorst, Philipp S","orcid":"0000-0002-5795-0133","last_name":"Schmalhorst","id":"309D50DA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Routier","first_name":"Françoise","full_name":"Routier, Françoise"}],"date_published":"2012-12-28T00:00:00Z","pmid":1,"acknowledgement":"This work was supported by the Deutsche Forschungsgemeinschaft.","date_created":"2018-12-11T11:48:34Z","intvolume":"       287","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","extern":"1","quality_controlled":"1","publist_id":"6852","month":"12","article_type":"original","volume":287,"date_updated":"2022-03-21T07:57:14Z","status":"public","abstract":[{"lang":"eng","text":"Fungal cell walls frequently contain a polymer of mannose and galactose called galactomannan. In the pathogenic filamentous fungus Aspergillus fumigatus, this polysaccharide is made of a linear mannan backbone with side chains of galactofuran and is anchored to the plasma membrane via a glycosylphosphatidylinositol or is covalently linked to the cell wall. To date, the biosynthesis and significance of this polysaccharide are unknown. The present data demonstrate that deletion of the Golgi UDP-galactofuranose transporter GlfB or the GDP-mannose transporter GmtA leads to the absence of galactofuran or galactomannan, respectively. This indicates that the biosynthesis of galactomannan probably occurs in the lumen of the Golgi apparatus and thus contrasts with the biosynthesis of other fungal cell wall polysaccharides studied to date that takes place at the plasma membrane. Transglycosylation of galactomannan from the membrane to the cell wall is hypothesized because both the cell wall-bound and membrane-bound polysaccharide forms are affected in the generated mutants. Considering the severe growth defect of the A. fumigatus GmtA-deficient mutant, proving this paradigm might provide new targets for antifungal therapy."}],"publication_status":"published","oa_version":"None","page":"44418 - 44424","day":"28","citation":{"ama":"Engel J, Schmalhorst PS, Routier F. Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose. <i>Journal of Biological Chemistry</i>. 2012;287(53):44418-44424. doi:<a href=\"https://doi.org/10.1074/jbc.M112.398321\">10.1074/jbc.M112.398321</a>","short":"J. Engel, P.S. Schmalhorst, F. Routier, Journal of Biological Chemistry 287 (2012) 44418–44424.","apa":"Engel, J., Schmalhorst, P. S., &#38; Routier, F. (2012). Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M112.398321\">https://doi.org/10.1074/jbc.M112.398321</a>","mla":"Engel, Jakob, et al. “Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-Mannose.” <i>Journal of Biological Chemistry</i>, vol. 287, no. 53, American Society for Biochemistry and Molecular Biology, 2012, pp. 44418–24, doi:<a href=\"https://doi.org/10.1074/jbc.M112.398321\">10.1074/jbc.M112.398321</a>.","ista":"Engel J, Schmalhorst PS, Routier F. 2012. Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose. Journal of Biological Chemistry. 287(53), 44418–44424.","ieee":"J. Engel, P. S. Schmalhorst, and F. Routier, “Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose,” <i>Journal of Biological Chemistry</i>, vol. 287, no. 53. American Society for Biochemistry and Molecular Biology, pp. 44418–44424, 2012.","chicago":"Engel, Jakob, Philipp S Schmalhorst, and Françoise Routier. “Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-Mannose.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2012. <a href=\"https://doi.org/10.1074/jbc.M112.398321\">https://doi.org/10.1074/jbc.M112.398321</a>."},"issue":"53","scopus_import":"1","external_id":{"pmid":["23139423"]},"title":"Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose","publication":"Journal of Biological Chemistry"},{"author":[{"last_name":"Engel","full_name":"Engel, Jakob","first_name":"Jakob"},{"id":"309D50DA-F248-11E8-B48F-1D18A9856A87","last_name":"Schmalhorst","orcid":"0000-0002-5795-0133","first_name":"Philipp S","full_name":"Schmalhorst, Philipp S"},{"last_name":"Dörk Bousset","first_name":"Thilo","full_name":"Dörk Bousset, Thilo"},{"last_name":"Ferrières","first_name":"Vincent","full_name":"Ferrières, Vincent"},{"first_name":"Françoise","full_name":"Routier, Françoise","last_name":"Routier"}],"_id":"3292","page":"33859 - 33868","oa_version":"None","publication_status":"published","date_published":"2009-12-04T00:00:00Z","day":"04","abstract":[{"lang":"eng","text":"Galactofuranose (Galf) containing molecules have been described at the cell surface of several eukaryotes and shown to contribute to the virulence of the parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated that a number of the surface glycoconjugates such as N-glycans or glycolipids are galactofuranosylated in the Golgi apparatus. This raises the question of how the substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized in the cytosol, translocates into the organelles of the secretory pathway. Here we report the first identification of a Golgi-localized nucleotide sugar transporter, named GlfB, with specificity for a UDP-Galf. In vitro transport assays established binding of UDP-Galf to GlfB and excluded transport of several other nucleotide sugars. Furthermore, the implication of glfB in the galactofuranosylation of A. fumigatus glycoconjugates and galactomannan was demonstrated by a targeted gene deletion approach. Our data reveal a direct connection between galactomannan and the organelles of the secretory pathway that strongly suggests that the cell wall-bound polysaccharide originates from its glycosylphosphatidylinositol-anchored form."}],"language":[{"iso":"eng"}],"doi":"10.1074/jbc.M109.070219 ","publisher":"American Society for Biochemistry and Molecular Biology","date_updated":"2021-01-12T07:42:26Z","year":"2009","status":"public","type":"journal_article","month":"12","quality_controlled":"1","publist_id":"3353","publication":"Journal of Biological Chemistry","volume":284,"title":"A single UDP galactofuranose transporter is required for galactofuranosylation in Aspergillus fumigatus","date_created":"2018-12-11T12:02:30Z","citation":{"chicago":"Engel, Jakob, Philipp S Schmalhorst, Thilo Dörk Bousset, Vincent Ferrières, and Françoise Routier. “A Single UDP Galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus Fumigatus.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2009. <a href=\"https://doi.org/10.1074/jbc.M109.070219 \">https://doi.org/10.1074/jbc.M109.070219 </a>.","ieee":"J. Engel, P. S. Schmalhorst, T. Dörk Bousset, V. Ferrières, and F. Routier, “A single UDP galactofuranose transporter is required for galactofuranosylation in Aspergillus fumigatus,” <i>Journal of Biological Chemistry</i>, vol. 284, no. 49. American Society for Biochemistry and Molecular Biology, pp. 33859–33868, 2009.","ista":"Engel J, Schmalhorst PS, Dörk Bousset T, Ferrières V, Routier F. 2009. A single UDP galactofuranose transporter is required for galactofuranosylation in Aspergillus fumigatus. Journal of Biological Chemistry. 284(49), 33859–33868.","apa":"Engel, J., Schmalhorst, P. S., Dörk Bousset, T., Ferrières, V., &#38; Routier, F. (2009). A single UDP galactofuranose transporter is required for galactofuranosylation in Aspergillus fumigatus. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M109.070219 \">https://doi.org/10.1074/jbc.M109.070219 </a>","mla":"Engel, Jakob, et al. “A Single UDP Galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus Fumigatus.” <i>Journal of Biological Chemistry</i>, vol. 284, no. 49, American Society for Biochemistry and Molecular Biology, 2009, pp. 33859–68, doi:<a href=\"https://doi.org/10.1074/jbc.M109.070219 \">10.1074/jbc.M109.070219 </a>.","short":"J. Engel, P.S. Schmalhorst, T. Dörk Bousset, V. Ferrières, F. Routier, Journal of Biological Chemistry 284 (2009) 33859–33868.","ama":"Engel J, Schmalhorst PS, Dörk Bousset T, Ferrières V, Routier F. A single UDP galactofuranose transporter is required for galactofuranosylation in Aspergillus fumigatus. <i>Journal of Biological Chemistry</i>. 2009;284(49):33859-33868. doi:<a href=\"https://doi.org/10.1074/jbc.M109.070219 \">10.1074/jbc.M109.070219 </a>"},"issue":"49","extern":"1","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":"       284"},{"date_updated":"2021-01-12T07:43:13Z","publisher":"Gottfried Wilhelm Leibniz Universität Hannover","year":"2009","status":"public","type":"dissertation","author":[{"full_name":"Philipp Schmalhorst","first_name":"Philipp S","id":"309D50DA-F248-11E8-B48F-1D18A9856A87","last_name":"Schmalhorst","orcid":"0000-0002-5795-0133"}],"_id":"3400","page":"1 - 72","date_published":"2009-08-13T00:00:00Z","publication_status":"published","day":"13","abstract":[{"lang":"eng","text":"Invasive fungal infections pose a serious threat to immunocompromised people. Most of these infections are caused by either Candida or Aspergillus species, with A. fumigatus being the predominant causative agent of Invasive Aspergillosis. Affected people comprise mainly haematopoietic stem cell or solid organ transplant patients who receive either high-dose corticosteroids or immunosuppressants. These risk factors predispose to the development of Invasive\nAspergillosis which is lethal in 20 to 80 % of the cases, largely due to insufficient efficacy of current antifungal therapy. Thus one major aim in current mycological research is the identification of new drug targets.\nThe polysaccharide-based fungal cell wall is both essential to fungi and absent from human cells which makes it appear an attractive new target. Notably, many components of the A. fumigatus cell wall, including the polysaccharide galactomannan, glycoproteins, and glycolipids, contain the unusual sugar galactofuranose (Galf). In contrast to the other cell wall monosaccharides, Galf does not occur on human cells but is known as component of cell surface molecules of many pathogenic bacteria and protozoa, such as Mycobacterium tuberculosis or Leishmania major. These molecules are often essential for virulence or viability of these organisms which suggested a possible role of Galf in the pathogenicity of A. fumigatus.\nTo address the importance of Galf in A. fumigatus, the key biosynthesis gene glfA, encoding UDPgalactopyranose mutase (UGM), was deleted. In different experimental approaches it was demonstrated that the absence of the glfA gene led to a complete loss of Galf-containing glycans.\nAnalysis of the DeltaglfA phenotype revealed growth and sporulation defects, reduced thermotolerance and an increased susceptibility to antifungal drugs. Electron Microscopy indicated a cell wall defect as a likely cause for the observed impairments. Furthermore, the virulence of the DeltaglfA mutant was found to be severely attenuated in a murine model of Invasive Aspergillosis.\nThe second focus of this study was laid on further elucidation of the galactofuranosylation pathway in A. fumigatus. In eukaryotes, a UDP-Galf transporter is likely required to transport UDP-Galf from the\ncytosol into the organelles of the secretory pathway, but no such activity had been described. Sixteen candidate genes were identified in the A. fumigatus genome of which one, glfB, was found in close proximity to the glfA gene. In vitro transport assays revealed specificity of GlfB for UDP-Galf suggesting that glfB encoded indeed a UDP-Galf transporter. The influence of glfB on\ngalactofuranosylation was determined by a DeltaglfB deletion mutant, which closely recapitulated the DeltaglfA phenotype and was likewise found to be completely devoid of Galf. It could be concluded that all galactofuranosylation processes in A. fumigatus occur in the secretory pathway, including the biosynthesis of the cell wall polysaccharide galactomannan whose subcellular origin was previously disputed.\n\nThus in the course of this study the first UDP-Galf specific nucleotide sugar transporter was identified and its requirement for galactofuranosylation in A. fumigatus demonstrated. Moreover, it was shown that blocking the galactofuranosylation pathway impaired virulence of A. fumigatus which suggests the UDP-Galf biosynthesis enzyme UGM as a target for new antifungal drugs."}],"date_created":"2018-12-11T12:03:07Z","citation":{"ista":"Schmalhorst PS. 2009. Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus fumigatus. Gottfried Wilhelm Leibniz Universität Hannover.","apa":"Schmalhorst, P. S. (2009). <i>Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus fumigatus</i>. Gottfried Wilhelm Leibniz Universität Hannover.","short":"P.S. Schmalhorst, Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus Fumigatus, Gottfried Wilhelm Leibniz Universität Hannover, 2009.","mla":"Schmalhorst, Philipp S. <i>Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus Fumigatus</i>. Gottfried Wilhelm Leibniz Universität Hannover, 2009, pp. 1–72.","ama":"Schmalhorst PS. Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus fumigatus. 2009:1-72.","chicago":"Schmalhorst, Philipp S. “Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus Fumigatus.” Gottfried Wilhelm Leibniz Universität Hannover, 2009.","ieee":"P. S. Schmalhorst, “Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus fumigatus,” Gottfried Wilhelm Leibniz Universität Hannover, 2009."},"extern":1,"month":"08","quality_controlled":0,"publist_id":"3058","main_file_link":[{"open_access":"0","url":"http://edok01.tib.uni-hannover.de/edoks/e01dh09/609861891.pdf"}],"title":"Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for the Pathogenic Fungus Aspergillus fumigatus"},{"status":"public","type":"journal_article","doi":"10.1128/EC.00065-08","date_updated":"2021-01-12T07:42:26Z","publisher":"American Society for Microbiology","year":"2008","date_published":"2008-06-13T00:00:00Z","page":"1268 - 1277","publication_status":"published","day":"13","abstract":[{"text":"The filamentous fungus Aspergillus fumigatus is responsible for a lethal disease called Invasive Aspergillosis that affects immunocompromised patients. This disease, like other human fungal diseases, is generally treated by compounds targeting the primary fungal cell membrane sterol. Recently, glucan synthesis inhibitors were added to the limited antifungal arsenal and encouraged the search for novel targets in cell wall biosynthesis. Although galactomannan is a major component of the A. fumigatus cell wall and extracellular matrix, the biosynthesis and role of galactomannan are currently unknown. By a targeted gene deletion approach, we demonstrate that UDP-galactopyranose mutase, a key enzyme of galactofuranose metabolism, controls the biosynthesis of galactomannan and galactofuranose containing glycoconjugates. The glfA deletion mutant generated in this study is devoid of galactofuranose and displays attenuated virulence in a low-dose mouse model of invasive aspergillosis that likely reflects the impaired growth of the mutant at mammalian body temperature. Furthermore, the absence of galactofuranose results in a thinner cell wall that correlates with an increased susceptibility to several antifungal agents. The UDP-galactopyranose mutase thus appears to be an appealing adjunct therapeutic target in combination with other drugs against A. fumigatus. Its absence from mammalian cells indeed offers a considerable advantage to achieve therapeutic selectivity. ","lang":"eng"}],"author":[{"orcid":"0000-0002-5795-0133","last_name":"Schmalhorst","id":"309D50DA-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp S","full_name":"Philipp Schmalhorst"},{"full_name":"Krappmann, Sven","first_name":"Sven","last_name":"Krappmann"},{"full_name":"Vervecken, Wouter","first_name":"Wouter","last_name":"Vervecken"},{"full_name":"Rohde, Manfred","first_name":"Manfred","last_name":"Rohde"},{"full_name":"Müller, Meike","first_name":"Meike","last_name":"Müller"},{"first_name":"Gerhard","full_name":"Braus, Gerhard H.","last_name":"Braus"},{"full_name":"Contreras, Roland","first_name":"Roland","last_name":"Contreras"},{"last_name":"Braun","full_name":"Braun, Armin","first_name":"Armin"},{"full_name":"Bakker, Hans","first_name":"Hans","last_name":"Bakker"},{"full_name":"Routier, Françoise H","first_name":"Françoise","last_name":"Routier"}],"_id":"3291","issue":"8","extern":1,"intvolume":"         7","date_created":"2018-12-11T12:02:29Z","citation":{"apa":"Schmalhorst, P. S., Krappmann, S., Vervecken, W., Rohde, M., Müller, M., Braus, G., … Routier, F. (2008). Contribution of galactofuranose to the virulence of the opportunistic pathogen Aspergillus fumigatus. <i>Eukaryotic Cell</i>. American Society for Microbiology. <a href=\"https://doi.org/10.1128/EC.00065-08\">https://doi.org/10.1128/EC.00065-08</a>","short":"P.S. Schmalhorst, S. Krappmann, W. Vervecken, M. Rohde, M. Müller, G. Braus, R. Contreras, A. Braun, H. Bakker, F. Routier, Eukaryotic Cell 7 (2008) 1268–1277.","ista":"Schmalhorst PS, Krappmann S, Vervecken W, Rohde M, Müller M, Braus G, Contreras R, Braun A, Bakker H, Routier F. 2008. Contribution of galactofuranose to the virulence of the opportunistic pathogen Aspergillus fumigatus. Eukaryotic Cell. 7(8), 1268–1277.","mla":"Schmalhorst, Philipp S., et al. “Contribution of Galactofuranose to the Virulence of the Opportunistic Pathogen Aspergillus Fumigatus.” <i>Eukaryotic Cell</i>, vol. 7, no. 8, American Society for Microbiology, 2008, pp. 1268–77, doi:<a href=\"https://doi.org/10.1128/EC.00065-08\">10.1128/EC.00065-08</a>.","ama":"Schmalhorst PS, Krappmann S, Vervecken W, et al. Contribution of galactofuranose to the virulence of the opportunistic pathogen Aspergillus fumigatus. <i>Eukaryotic Cell</i>. 2008;7(8):1268-1277. doi:<a href=\"https://doi.org/10.1128/EC.00065-08\">10.1128/EC.00065-08</a>","chicago":"Schmalhorst, Philipp S, Sven Krappmann, Wouter Vervecken, Manfred Rohde, Meike Müller, Gerhard Braus, Roland Contreras, Armin Braun, Hans Bakker, and Françoise Routier. “Contribution of Galactofuranose to the Virulence of the Opportunistic Pathogen Aspergillus Fumigatus.” <i>Eukaryotic Cell</i>. American Society for Microbiology, 2008. <a href=\"https://doi.org/10.1128/EC.00065-08\">https://doi.org/10.1128/EC.00065-08</a>.","ieee":"P. S. Schmalhorst <i>et al.</i>, “Contribution of galactofuranose to the virulence of the opportunistic pathogen Aspergillus fumigatus,” <i>Eukaryotic Cell</i>, vol. 7, no. 8. American Society for Microbiology, pp. 1268–1277, 2008."},"publication":"Eukaryotic Cell","volume":7,"title":"Contribution of galactofuranose to the virulence of the opportunistic pathogen Aspergillus fumigatus","month":"06","quality_controlled":0,"publist_id":"3354"}]