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Renata Zuber, Michaela Norum, Yiwen Wang, Kathrin Oehl, Nicole Gehring, Davide Accardi, Slawomir Bartozsewski, Jürgen Berger, Matthias Flötenmeyer, Bernard Moussian
The ABC transporter Snu and the extracellular protein Snsl cooperate in the formation of the lipid-based inward and outward barrier in the skin of Drosophila.
Eur J Cell Biol, Art. No. doi: 10.1016/j.ejcb.2017.12.003 (2018)
PubMed Source   

Lipids in extracellular matrices (ECM) contribute to barrier function and stability of epithelial tissues such as the pulmonary alveoli and the skin. In insects, skin waterproofness depends on the outermost layer of the extracellular cuticle termed envelope that contains cuticulin, an unidentified water-repellent complex molecule composed of proteins, lipids and catecholamines. Based on live-imaging analyses of fruit fly larvae, we find that initially envelope units are assembled within putative vesicles harbouring the ABC transporter Snu and the extracellular protein Snsl. In a second step, the content of these vesicles is distributed to cuticular lipid-transporting nanotubes named pore canals and to the cuticle surface in dependence of Snu function. Consistently, the surface of snu and snsl mutant larvae is depleted from lipids and cuticulin. By consequence, these animals suffer uncontrolled water loss and penetration of xenobiotics. Our data allude to a two-step model of envelope i.e. barrier formation. The proposed mechanism in principle parallels the events occurring during differentiation of the lipid-based ECM by keratinocytes in the vertebrate skin suggesting establishment of analogous mechanisms of skin barrier formation in vertebrates and invertebrates.
@article{Zuber7027,
author={Renata Zuber, Michaela Norum, Yiwen Wang, Kathrin Oehl, Nicole Gehring, Davide Accardi, Slawomir Bartozsewski, Jürgen Berger, Matthias Flötenmeyer, Bernard Moussian},
title={The ABC transporter Snu and the extracellular protein Snsl cooperate in the formation of the lipid-based inward and outward barrier in the skin of Drosophila.},
journal={European journal of cell biology},
volume={},
pages={1--1},
year=2018
}

Michael Bugiel, Aniruddha Mitra, Salvatore Girardo, Stefan Diez, Erik Schäffer
Measuring Microtubule Supertwist and Defects by Three-Dimensional-Force-Clamp Tracking of Single Kinesin-1 Motors.
Nano Lett, 18(2) 1290-1295 (2018)
PubMed Source   

Three-dimensional (3D) nanometer tracking of single biomolecules provides important information about their biological function. However, existing microscopy approaches often have only limited spatial or temporal precision and do not allow the application of defined loads. Here, we developed and applied a high-precision 3D-optical-tweezers force clamp to track in vitro the 3D motion of single kinesin-1 motor proteins along microtubules. To provide the motors with unimpeded access to the whole microtubule lattice, we mounted the microtubules on topographic surface features generated by UV-nanoimprint lithography. Because kinesin-1 motors processively move along individual protofilaments, we could determine the number of protofilaments the microtubules were composed of by measuring the helical pitches of motor movement on supertwisted microtubules. Moreover, we were able to identify defects in microtubules, most likely arising from local changes in the protofilament number. While it is hypothesized that microtubule supertwist and defects can severely influence the function of motors and other microtubule-associated proteins, the presented method allows for the first time to fully map the microtubule lattice in situ. This mapping allows the correlation of motor-filament interactions with the microtubule fine-structure. With the additional ability to apply loads, we expect our 3D-optical-tweezers force clamp to become a valuable tool for obtaining a wide range of information from other biological systems, inaccessible by two-dimensional and/or ensemble measurements.
@article{Bugiel7069,
author={Michael Bugiel, Aniruddha Mitra, Salvatore Girardo, Stefan Diez, Erik Schäffer},
title={Measuring Microtubule Supertwist and Defects by Three-Dimensional-Force-Clamp Tracking of Single Kinesin-1 Motors.},
journal={Nano letters},
volume={18},
issue ={2},
pages={1290--1295},
year=2018
}

J P Joos, A R Saadatmand, C Schnabel, Ivana Viktorinová, Thomas Brand, M Kramer, S Nattel, D Dobrev, Pavel Tomancak, J Backs, P Kleinbongard, G Heusch, K Lorenz, E Koch, S Weber, A El-Armouche
Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila.
Sci Rep, 8(1) 2940-2940 (2018)
PubMed Source   

Histone H3 serine 28 (H3S28) phosphorylation and de-repression of polycomb repressive complex (PRC)-mediated gene regulation is linked to stress conditions in mitotic and post-mitotic cells. To better understand the role of H3S28 phosphorylation in vivo, we studied a Drosophila strain with ectopic expression of constitutively-activated H3S28A, which prevents PRC2 binding at H3S28, thus mimicking H3S28 phosphorylation. H3S28A mutants showed prolonged life span and improved resistance against starvation and paraquat-induced oxidative stress. Morphological and functional analysis of heart tubes revealed smaller luminal areas and thicker walls accompanied by moderately improved cardiac function after acute stress induction. Whole-exome deep gene-sequencing from isolated heart tubes revealed phenotype-corresponding changes in longevity-promoting and myotropic genes. We also found changes in genes controlling mitochondrial biogenesis and respiration. Analysis of mitochondrial respiration from whole flies revealed improved efficacy of ATP production with reduced electron transport-chain activity. Finally, we analyzed posttranslational modification of H3S28 in an experimental heart failure model and observed increased H3S28 phosphorylation levels in HF hearts. Our data establish a critical role of H3S28 phosphorylation in vivo for life span, stress resistance, cardiac and mitochondrial function in Drosophila. These findings may pave the way for H3S28 phosphorylation as a putative target to treat stress-related disorders such as heart failure.
@article{Joos7067,
author={J P Joos, A R Saadatmand, C Schnabel, Ivana Viktorinová, Thomas Brand, M Kramer, S Nattel, D Dobrev, Pavel Tomancak, J Backs, P Kleinbongard, G Heusch, K Lorenz, E Koch, S Weber, A El-Armouche},
title={Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila.},
journal={Scientific reports},
volume={8},
issue ={1},
pages={2940--2940},
year=2018
}

Lara Marrone, Ina Poser, Ian Casci, Julia Japtok, Peter Reinhardt, Antje Janosch, Cordula Andree, Hyun-Ok Kate Lee, Claudia Moebius, Ellen Koerner, Lydia Reinhardt, Maria Elena Cicardi, Karl Hackmann, Barbara Klink, Angelo Poletti, Simon Alberti, Marc Bickle, Andreas Hermann, Udai Pandey, Anthony Hyman, Jared Sterneckert
Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy.
Stem Cell Reports, 10(2) 375-389 (2018)
PubMed Source   

Perturbations in stress granule (SG) dynamics may be at the core of amyotrophic lateral sclerosis (ALS). Since SGs are membraneless compartments, modeling their dynamics in human motor neurons has been challenging, thus hindering the identification of effective therapeutics. Here, we report the generation of isogenic induced pluripotent stem cells carrying wild-type and P525L FUS-eGFP. We demonstrate that FUS-eGFP is recruited into SGs and that P525L profoundly alters their dynamics. With a screening campaign, we demonstrate that PI3K/AKT/mTOR pathway inhibition increases autophagy and ameliorates SG phenotypes linked to P525L FUS by reducing FUS-eGFP recruitment into SGs. Using a Drosophila model of FUS-ALS, we corroborate that induction of autophagy significantly increases survival. Finally, by screening clinically approved drugs for their ability to ameliorate FUS SG phenotypes, we identify a number of brain-penetrant anti-depressants and anti-psychotics that also induce autophagy. These drugs could be repurposed as potential ALS treatments.
@article{Marrone7052,
author={Lara Marrone, Ina Poser, Ian Casci, Julia Japtok, Peter Reinhardt, Antje Janosch, Cordula Andree, Hyun-Ok Kate Lee, Claudia Moebius, Ellen Koerner, Lydia Reinhardt, Maria Elena Cicardi, Karl Hackmann, Barbara Klink, Angelo Poletti, Simon Alberti, Marc Bickle, Andreas Hermann, Udai Pandey, Anthony Hyman, Jared Sterneckert},
title={Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy.},
journal={Stem cell reports},
volume={10},
issue ={2},
pages={375--389},
year=2018
}

Matthäus Mittasch, Peter Gross, Michael Nestler, Anatol W Fritsch, Christiane Iserman, Mrityunjoy Kar, Matthias Munder, Axel Voigt, Simon Alberti, Stephan W. Grill, Moritz Kreysing
Non-invasive perturbations of intracellular flow reveal physical principles of cell organization.
Nat Cell Biol, Art. No. doi: 10.1038/s41556-017-0032-9 (2018)
PubMed Source   

Recent advances in cell biology enable precise molecular perturbations. The spatiotemporal organization of cells and organisms, however, also depends on physical processes such as diffusion or cytoplasmic flows, and strategies to perturb physical transport inside cells are not yet available. Here, we demonstrate focused-light-induced cytoplasmic streaming (FLUCS). FLUCS is local, directional, dynamic, probe-free, physiological, and is even applicable through rigid egg shells or cell walls. We explain FLUCS via time-dependent modelling of thermoviscous flows. Using FLUCS, we demonstrate that cytoplasmic flows drive partitioning-defective protein (PAR) polarization in Caenorhabditis elegans zygotes, and that cortical flows are sufficient to transport PAR domains and invert PAR polarity. In addition, we find that asymmetric cell division is a binary decision based on gradually varying PAR polarization states. Furthermore, the use of FLUCS for active microrheology revealed a metabolically induced fluid-to-solid transition of the yeast cytoplasm. Our findings establish how a wide range of transport-dependent models of cellular organization become testable by FLUCS.
@article{Mittasch7055,
author={Matthäus Mittasch, Peter Gross, Michael Nestler, Anatol W Fritsch, Christiane Iserman, Mrityunjoy Kar, Matthias Munder, Axel Voigt, Simon Alberti, Stephan W. Grill, Moritz Kreysing},
title={Non-invasive perturbations of intracellular flow reveal physical principles of cell organization.},
journal={Nature cell biology},
volume={},
pages={null--null},
year=2018
}

Matthäus Mittasch, Peter Gross, Michael Nestler, Anatol W Fritsch, Christiane Iserman, Mrityunjoy Kar, Matthias Munder, Axel Voigt, Simon Alberti, Stephan W. Grill, Moritz Kreysing
How to apply FLUCS in single cells and living embryos
Protocol Exchange, Art. No. doi:10.1038/protex.2017.157 (2018)
Source  

@article{Mittasch7057,
author={Matthäus Mittasch, Peter Gross, Michael Nestler, Anatol W Fritsch, Christiane Iserman, Mrityunjoy Kar, Matthias Munder, Axel Voigt, Simon Alberti, Stephan W. Grill, Moritz Kreysing},
title={How to apply FLUCS in single cells and living embryos},
journal={Protocol Exchange},
volume={},
pages={null--null},
year=2018
}

Ronald Sluys, Miquel Vila-Farré, Jochen Rink, John E. J. Rasko
An intriguing, new planarian species from Tasmania, with a discussion on protandry in triclad flatworms (Platyhelminthes, Tricladida)
Acta Zool, Art. No. doi: 10.1111/azo.12243 (2018)
Source   

An account is given of an unusual new species of freshwater planarian from the Hartz Mountains in Tasmania, Australia, Romankenkius flaccidus Sluys, sp. nov. The species is characterized, among other features, by an asymmetrical penis papilla, an extremely large, elongated copulatory bursa, and by the absence of testes in animals with fully developed male and female copulatory apparatus. Instigated by the sexual cycle of this new species, the study opportunely reviews whether planarian flatworms generally are simultaneous or sequential—in particular protandrous—hermaphrodites. It is concluded that real protandry does not occur in triclads and that even less extreme cases of sexual segregation, such as complete reduction of the testes or the more or less complete separation of male and female functionality as present in some species, have only sparsely and convergently evolved within the group of the triclad flatworms.
@article{Sluys7068,
author={Ronald Sluys, Miquel Vila-Farré, Jochen Rink, John E. J. Rasko},
title={An intriguing, new planarian species from Tasmania, with a discussion on protandry in triclad flatworms (Platyhelminthes, Tricladida)},
journal={Acta Zoologica},
volume={},
pages={1--1},
year=2018
}

Simon Alberti
Guilty by Association: Mapping Out the Molecular Sociology of Droplet Compartments.
Mol Cell, 69(3) 349-351 (2018)
PubMed Source   

The molecular interactions driving the formation of stress-inducible granules have largely remained unknown. In two recent papers, Youn et al. (2018) and Markmiller et al. (2018) use proximity labeling proteomics to map out the protein interactome of stress-inducible ribonucleoprotein granules.
@article{Alberti7064,
author={Simon Alberti},
title={Guilty by Association: Mapping Out the Molecular Sociology of Droplet Compartments.},
journal={Molecular cell},
volume={69},
issue ={3},
pages={349--351},
year=2018
}

Markus Grohme, Siegfried Schloissnig, Andrei Rozanski, Martin Pippel, George Robert Young, Sylke Winkler, Holger Brandl, Ian Henry, Andreas Dahl, Sean Powell, Michael Hiller, Eugene Myers, Jochen Rink
The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms.
Nature, 554(7690) 56-61 (2018)
PubMed Source   

The planarian Schmidtea mediterranea is an important model for stem cell research and regeneration, but adequate genome resources for this species have been lacking. Here we report a highly contiguous genome assembly of S. mediterranea, using long-read sequencing and a de novo assembler (MARVEL) enhanced for low-complexity reads. The S. mediterranea genome is highly polymorphic and repetitive, and harbours a novel class of giant retroelements. Furthermore, the genome assembly lacks a number of highly conserved genes, including critical components of the mitotic spindle assembly checkpoint, but planarians maintain checkpoint function. Our genome assembly provides a key model system resource that will be useful for studying regeneration and the evolutionary plasticity of core cell biological mechanisms.
@article{Grohme7065,
author={Markus Grohme, Siegfried Schloissnig, Andrei Rozanski, Martin Pippel, George Robert Young, Sylke Winkler, Holger Brandl, Ian Henry, Andreas Dahl, Sean Powell, Michael Hiller, Eugene Myers, Jochen Rink},
title={The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms.},
journal={Nature},
volume={554},
issue ={7690},
pages={56--61},
year=2018
}

Mukesh Kumar, Shai Joseph, Martina Augsburg, Aliona Bogdanova, David N. Drechsel, Nadine Vastenhouw, Frank Buchholz, Marc Gentzel, Andrej Shevchenko
MS Western, a Method of Multiplexed Absolute Protein Quantification is a Practical Alternative to Western Blotting.
Mol Cell Proteomics, 17(2) 384-396 (2018)
PubMed Source   

Absolute quantification of proteins elucidates the molecular composition, regulation and dynamics of multiprotein assemblies and networks. Here we report on a method termed MS Western that accurately determines the molar abundance of dozens of user-selected proteins at the subfemtomole level in whole cell or tissue lysates without metabolic or chemical labeling and without using specific antibodies. MS Western relies on GeLC-MS/MS and quantifies proteins by in-gel codigestion with an isotopically labeled QconCAT protein chimera composed of concatenated proteotypic peptides. It requires no purification of the chimera and relates the molar abundance of all proteotypic peptides to a single reference protein. In comparative experiments, MS Western outperformed immunofluorescence Western blotting by the protein detection specificity, linear dynamic range and sensitivity of protein quantification. To validate MS Western in an in vivo experiment, we quantified the molar content of zebrafish core histones H2A, H2B, H3 and H4 during ten stages of early embryogenesis. Accurate quantification (CV<10%) corroborated the anticipated histones equimolar stoichiometry and revealed an unexpected trend in their total abundance.
@article{Kumar6999,
author={Mukesh Kumar, Shai Joseph, Martina Augsburg, Aliona Bogdanova, David N. Drechsel, Nadine Vastenhouw, Frank Buchholz, Marc Gentzel, Andrej Shevchenko},
title={MS Western, a Method of Multiplexed Absolute Protein Quantification is a Practical Alternative to Western Blotting.},
journal={Molecular & cellular proteomics : MCP},
volume={17},
issue ={2},
pages={384--396},
year=2018
}