@article{802, abstract = {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.}, author = {Engel, Jakob and Schmalhorst, Philipp S and Kruger, Anke and Muller, Christina and Buettner, Falk and Routier, Françoise}, journal = {Glycobiology}, number = {12}, pages = {1423 -- 1430}, publisher = {Oxford University Press}, title = {{Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis}}, doi = {10.1093/glycob/cwv059}, volume = {25}, year = {2015}, } @article{1566, abstract = {Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease.}, author = {Gómez Sicilia, Àngel and Sikora, Mateusz K and Cieplak, Marek and Carrión Vázquez, Mariano}, journal = {PLoS Computational Biology}, number = {10}, publisher = {Public Library of Science}, title = {{An exploration of the universe of polyglutamine structures}}, doi = {10.1371/journal.pcbi.1004541}, volume = {11}, year = {2015}, } @misc{9714, author = {Gómez Sicilia, Àngel and Sikora, Mateusz K and Cieplak, Marek and Carrión Vázquez, Mariano}, publisher = {Public Library of Science }, title = {{An exploration of the universe of polyglutamine structures - submission to PLOS journals}}, doi = {10.1371/journal.pcbi.1004541.s001}, year = {2015}, } @article{1537, abstract = {3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype.}, author = {Ruprecht, Verena and Wieser, Stefan and Callan Jones, Andrew and Smutny, Michael and Morita, Hitoshi and Sako, Keisuke and Barone, Vanessa and Ritsch Marte, Monika and Sixt, Michael K and Voituriez, Raphaël and Heisenberg, Carl-Philipp J}, journal = {Cell}, number = {4}, pages = {673 -- 685}, publisher = {Cell Press}, title = {{Cortical contractility triggers a stochastic switch to fast amoeboid cell motility}}, doi = {10.1016/j.cell.2015.01.008}, volume = {160}, year = {2015}, } @article{10815, abstract = {In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the “tool-kit genes” essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool-kit genes may cause congenital diseases involving morphological abnormalities. This link between genes and abnormal morphological phenotypes underscores the importance of understanding how cells behave and contribute to morphogenesis as a result of gene function. Recent improvements in live imaging and in quantitative analyses of cellular dynamics will advance our understanding of the cellular pathogenesis of congenital diseases associated with aberrant morphologies. In these studies, it is critical to select an appropriate model organism for the particular phenomenon of interest.}, author = {Hashimoto, Masakazu and Morita, Hitoshi and Ueno, Naoto}, issn = {0914-3505}, journal = {Congenital Anomalies}, keywords = {Developmental Biology, Embryology, General Medicine, Pediatrics, Perinatology, and Child Health}, number = {1}, pages = {1--7}, publisher = {Wiley}, title = {{Molecular and cellular mechanisms of development underlying congenital diseases}}, doi = {10.1111/cga.12039}, volume = {54}, year = {2014}, }