Sort by
Showing 21 to 30 of 2,331 entries
Show entries

Ilia Zhernov, Stefan Diez, Marcus Braun, Zdenek Lansky
Intrinsically Disordered Domain of Kinesin-3 Kif14 Enables Unique Functional Diversity.
Curr Biol, Art. No. doi: 10.1016/j.cub.2020.06.039 (2020)
PubMed Source   

In addition to their force-generating motor domains, kinesin motor proteins feature various accessory domains enabling them to fulfill a variety of functions in the cell. Human kinesin-3, Kif14, localizes to the midbody of the mitotic spindle and is involved in the progression of cytokinesis. The specific motor properties enabling Kif14's cellular functions, however, remain unknown. Here, we show in vitro that the intrinsically disordered N-terminal domain of Kif14 enables unique functional diversity of the kinesin. Using single molecule TIRF microscopy, we found that Kif14 exists either as a diffusible monomer or as processive dimer and that the disordered domain (1) enables diffusibility of the monomeric Kif14, (2) renders the dimeric Kif14 super-processive and enables the kinesin to pass through highly crowded areas, (3) enables robust, autonomous Kif14 tracking of growing microtubule tips, independent of microtubule end-binding (EB) proteins, and (4) is sufficient to enable crosslinking of parallel microtubules and necessary to enable Kif14-driven sliding of antiparallel ones. We explain these features of Kif14 by the observed diffusible interaction of the disordered domain with the microtubule lattice and the observed increased affinity of the disordered domain for GTP-bound tubulin. We suggest that the disordered domain tethers the motor domain to the microtubule providing a diffusible foothold and a regulatory hub, tuning the kinesin's interaction with microtubules. Our findings thus exemplify pliable protein tethering as a fundamental mechanism of molecular motor regulation.
@article{Zhernov7712,
author={Ilia Zhernov, Stefan Diez, Marcus Braun, Zdenek Lansky},
title={Intrinsically Disordered Domain of Kinesin-3 Kif14 Enables Unique Functional Diversity.},
journal ={Current biology : CB},
volume={},
pages={1--1},
year=2020
}

Nandini Asokan, Stephan Daetwyler, Stefanie N Bernas, Christopher Schmied, Steffen Vogler, Katrin Lambert, Manja Wobus, Martin Wermke, Gerd Kempermann, Jan Huisken, Michael Brand, Martin Bornhäuser
Long-term in vivo imaging reveals tumor-specific dissemination and captures host tumor interaction in zebrafish xenografts.
Sci Rep, 10(1) Art. No. 13254 (2020)
PubMed Source   

Understanding mechanisms mediating tumor metastasis is crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track metastatic cells in real time using selective plane illumination microscopy (SPIM) for up to 30 h. Injected human leukemic and breast cancer cells exhibited cell-type specific patterns of intravascular distribution with leukemic cells moving faster than breast cancer cells. Tracking of tumor cells from high-resolution images revealed acute differences in intravascular speed and distance covered by cells. While the majority of injected breast cancer cells predominantly adhered to nearby vasculature, about 30% invaded the non-vascularized tissue, reminiscent of their metastatic phenotype. Survival of the injected tumor cells appeared to be partially inhibited and time-lapse imaging showed a possible role for host macrophages of the recipient embryos. Leukemic cell dissemination could be effectively blocked by pharmacological ROCK1 inhibition using Fasudil. These observations, and the ability to image several embryos simultaneously, support the use of eZXM and SPIM imaging as a functional screening platform to identify compounds that suppress cancer cell spread and invasion.
@article{Asokan7727,
author={Nandini Asokan, Stephan Daetwyler, Stefanie N Bernas, Christopher Schmied, Steffen Vogler, Katrin Lambert, Manja Wobus, Martin Wermke, Gerd Kempermann, Jan Huisken, Michael Brand, Martin Bornhäuser},
title={Long-term in vivo imaging reveals tumor-specific dissemination and captures host tumor interaction in zebrafish xenografts.},
journal ={Scientific reports},
volume={10},
issue ={1},
pages={null--null},
year=2020
}

Michael Heide, Christiane Haffner, Ayako Y Murayama, Yoko Kurotaki, Haruka Shinohara, Hideyuki Okano, Erika Sasaki, Wieland Huttner
Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset.
Science, 369(6503) 546-550 (2020)
PubMed Source   

The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common marmoset under control of the gene's own (human) promoter increased the numbers of basal radial glia progenitors in the marmoset outer subventricular zone, increased the numbers of upper-layer neurons, enlarged the neocortex, and induced its folding. Thus, the human-specific ARHGAP11B drives changes in development in the nonhuman primate marmoset that reflect the changes in evolution that characterize human neocortical development.
@article{Heide7693,
author={Michael Heide, Christiane Haffner, Ayako Y Murayama, Yoko Kurotaki, Haruka Shinohara, Hideyuki Okano, Erika Sasaki, Wieland Huttner},
title={Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset.},
journal ={Science (New York, N.Y.)},
volume={369},
issue ={6503},
pages={546--550},
year=2020
}

Dror Sever, Anne Grapin-Botton
Regeneration of the pancreas: proliferation and cellular conversion of surviving cells.
Curr Opin Genet Dev, 64 84-93 (2020)
PubMed Source   

The most common pancreas-related disorders are diabetes, pancreatitis and different types of pancreatic cancers. Diabetes is a chronic condition which results from insufficient functional β-cell mass, either as a result of an autoimmune destruction of insulin producing β-cells, or as their death or de-differentiation following years of hyperactivity to compensate for insulin resistance. Chronic pancreatitis leads to cell death and can develop into diabetes or pancreatic cancer. To stimulate regeneration in such pathologies, it is of high importance to evaluate the endogenous regeneration capacity of the pancreas, to understand the conditions needed to trigger it, and to investigate the cellular and molecular regenerative responses. This short review focuses on observations made in the last 2 years on the mechanisms enhancing pancreatic cell proliferation, notably new combinations of pharmacological agents, as well as those triggering cellular conversion.
@article{Sever7725,
author={Dror Sever, Anne Grapin-Botton},
title={Regeneration of the pancreas: proliferation and cellular conversion of surviving cells.},
journal ={Current opinion in genetics & development},
volume={64},
pages={84--93},
year=2020
}

Hannah E Walters, Maximina H Yun
Rising from the ashes: cellular senescence in regeneration.
Curr Opin Genet Dev, 64 94-100 (2020)
PubMed Source   

Cellular senescence has recently become causally implicated in pathological ageing. Hence, a great deal of research is currently dedicated towards developing senolytic agents to selectively kill senescent cells. However, senescence also plays important roles in a range of physiological processes including during organismal development, providing a barrier to tumorigenesis and in limiting fibrosis. Recent evidence also suggests a role for senescence in coordinating tissue remodelling and in the regeneration of complex structures. Through its non-cell-autonomous effects, a transient induction of senescence may create a permissive environment for remodelling or regeneration through promoting local proliferation, cell plasticity, tissue patterning, balancing growth, or indirectly through finely tuned interactions with infiltrating immune mediators. A careful analysis of the beneficial roles of cellular senescence may provide insights into important physiological processes as well as informing strategies to counteract its detrimental consequences in ageing and disease.
@article{Walters7726,
author={Hannah E Walters, Maximina H Yun},
title={Rising from the ashes: cellular senescence in regeneration.},
journal ={Current opinion in genetics & development},
volume={64},
pages={94--100},
year=2020
}

David Jebb, Zixia Huang, Martin Pippel, Graham M Hughes, Ksenia Lavrichenko, Paolo Devanna, Sylke Winkler, Lars S Jermiin, Emilia C Skirmuntt, Aris Katzourakis, Lucy Burkitt-Gray, David A Ray, Kevin F. Sullivan, Juliana G. Roscito, Bogdan Kirilenko, Liliana M Dávalos, Angelique P Corthals, Megan L Power, Gareth Jones, Roger D Ransome, Dina K N Dechmann, Andrea G Locatelli, Sébastien J Puechmaille, Olivier Fedrigo, Erich D Jarvis, Michael Hiller, Sonja Vernes, Eugene W Myers, Emma Teeling
Six reference-quality genomes reveal evolution of bat adaptations.
Nature, 583(7817) 578-584 (2020)
PubMed Source   

Bats possess extraordinary adaptations, including flight, echolocation, extreme longevity and unique immunity. High-quality genomes are crucial for understanding the molecular basis and evolution of these traits. Here we incorporated long-read sequencing and state-of-the-art scaffolding protocols1 to generate, to our knowledge, the first reference-quality genomes of six bat species (Rhinolophus ferrumequinum, Rousettus aegyptiacus, Phyllostomus discolor, Myotis myotis, Pipistrellus kuhlii and Molossus molossus). We integrated gene projections from our 'Tool to infer Orthologs from Genome Alignments' (TOGA) software with de novo and homology gene predictions as well as short- and long-read transcriptomics to generate highly complete gene annotations. To resolve the phylogenetic position of bats within Laurasiatheria, we applied several phylogenetic methods to comprehensive sets of orthologous protein-coding and noncoding regions of the genome, and identified a basal origin for bats within Scrotifera. Our genome-wide screens revealed positive selection on hearing-related genes in the ancestral branch of bats, which is indicative of laryngeal echolocation being an ancestral trait in this clade. We found selection and loss of immunity-related genes (including pro-inflammatory NF-κB regulators) and expansions of anti-viral APOBEC3 genes, which highlights molecular mechanisms that may contribute to the exceptional immunity of bats. Genomic integrations of diverse viruses provide a genomic record of historical tolerance to viral infection in bats. Finally, we found and experimentally validated bat-specific variation in microRNAs, which may regulate bat-specific gene-expression programs. Our reference-quality bat genomes provide the resources required to uncover and validate the genomic basis of adaptations of bats, and stimulate new avenues of research that are directly relevant to human health and disease1.
@article{Jebb7723,
author={David Jebb, Zixia Huang, Martin Pippel, Graham M Hughes, Ksenia Lavrichenko, Paolo Devanna, Sylke Winkler, Lars S Jermiin, Emilia C Skirmuntt, Aris Katzourakis, Lucy Burkitt-Gray, David A Ray, Kevin F. Sullivan, Juliana G. Roscito, Bogdan Kirilenko, Liliana M Dávalos, Angelique P Corthals, Megan L Power, Gareth Jones, Roger D Ransome, Dina K N Dechmann, Andrea G Locatelli, Sébastien J Puechmaille, Olivier Fedrigo, Erich D Jarvis, Michael Hiller, Sonja Vernes, Eugene W Myers, Emma Teeling},
title={Six reference-quality genomes reveal evolution of bat adaptations.},
journal ={Nature},
volume={583},
issue ={7817},
pages={578--584},
year=2020
}

Laura Mediani, Veronica Galli, Arianna D Carrà, Ilaria Bigi, Jonathan Vinet, Massimo Ganassi, Francesco Antoniani, Tatiana Tiago, Marco Cimino, Daniel Mateju, Cristina Cereda, Orietta Pansarasa, Simon Alberti, Jessica Mandrioli, Serena Carra
BAG3 and BAG6 differentially affect the dynamics of stress granules by targeting distinct subsets of defective polypeptides released from ribosomes.
Cell Stress Chaperones, Art. No. doi: 10.1007/s12192-020-01141-w (2020)
PubMed Source   

Stress granules (SGs) are dynamic ribonucleoprotein granules induced by environmental stresses. They play an important role in the stress response by integrating mRNA stability, translation, and signaling pathways. Recent work has connected SG dysfunction to neurodegenerative diseases. In these diseases, SG dynamics are impaired because of mutations in SG proteins or protein quality control factors. Impaired SG dynamics and delayed SG dissolution have also been observed for SGs that accumulate misfolding-prone defective ribosomal products (DRiPs). DRiP accumulation inside SGs is controlled by a surveillance system referred to as granulostasis and encompasses the molecular chaperones VCP and the HSPB8-BAG3-HSP70 complex. BAG3 is a member of the BAG family of proteins, which includes five additional members. One of these proteins, BAG6, is functionally related to BAG3 and able to assist degradation of DRiPs. However, whether BAG6 is involved in granulostasis is unknown. We report that BAG6 is not recruited into SGs induced by different types of stress, nor does it affect SG dynamics. BAG6 also does not replace BAG3's function in SG granulostasis. We show that BAG3 and BAG6 target different subsets of DRiPs, and BAG3 binding to DRiPs is mediated by HSPB8 and HSP70. Our data support the idea that SGs are sensitive to BAG3-HSP70-bound DRiPs but not to BAG6-bound DRiPs. Additionally, only BAG3 is strongly upregulated in the stress recovery phase, when SGs dissolve. These data exclude a role for BAG6 in granulostasis and point to a more specialized function in the clearance of a specific subset of DRiPs.
@article{Mediani7719,
author={Laura Mediani, Veronica Galli, Arianna D Carrà, Ilaria Bigi, Jonathan Vinet, Massimo Ganassi, Francesco Antoniani, Tatiana Tiago, Marco Cimino, Daniel Mateju, Cristina Cereda, Orietta Pansarasa, Simon Alberti, Jessica Mandrioli, Serena Carra},
title={BAG3 and BAG6 differentially affect the dynamics of stress granules by targeting distinct subsets of defective polypeptides released from ribosomes.},
journal ={Cell stress & chaperones},
volume={},
pages={1--1},
year=2020
}

Keiichi Katsumoto, Anne Grapin-Botton
Nutrients men-TOR β-Cells to Adulthood.
Dev Cell, 54(2) 140-141 (2020)
PubMed Source   

A major trigger of adult β-cell insulin secretion is glucose. In a recent issue of Cell Metabolism, Helman and colleagues show that in fetuses insulin secretion depends on the activation of mTOR by amino acids and that reducing amino acids promotes maturation of β-cells derived from pluripotent stem cells.
@article{Katsumoto7716,
author={Keiichi Katsumoto, Anne Grapin-Botton},
title={Nutrients men-TOR β-Cells to Adulthood.},
journal ={Developmental cell},
volume={54},
issue ={2},
pages={140--141},
year=2020
}

Christoph Zechner, Elisa Nerli, Caren Norden
Stochasticity and determinism in cell fate decisions.
Development, 147(14) Art. No. dev181495 (2020)
PubMed Source   

During development, cells need to make decisions about their fate in order to ensure that the correct numbers and types of cells are established at the correct time and place in the embryo. Such cell fate decisions are often classified as deterministic or stochastic. However, although these terms are clearly defined in a mathematical sense, they are sometimes used ambiguously in biological contexts. Here, we provide some suggestions on how to clarify the definitions and usage of the terms stochastic and deterministic in biological experiments. We discuss the frameworks within which such clear definitions make sense and highlight when certain ambiguity prevails. As an example, we examine how these terms are used in studies of neuronal cell fate decisions and point out areas in which definitions and interpretations have changed and matured over time. We hope that this Review will provide some clarification and inspire discussion on the use of terminology in relation to fate decisions.
@article{Zechner7714,
author={Christoph Zechner, Elisa Nerli, Caren Norden},
title={Stochasticity and determinism in cell fate decisions.},
journal ={Development (Cambridge, England)},
volume={147},
issue ={14},
pages={1--1},
year=2020
}

David Oriola, Frank Jülicher, Jan Brugués
Active forces shape the metaphase spindle through a mechanical instability.
Proc Natl Acad Sci U.S.A., 117(28) 16154-16159 (2020)
PubMed Source   

The metaphase spindle is a dynamic structure orchestrating chromosome segregation during cell division. Recently, soft matter approaches have shown that the spindle behaves as an active liquid crystal. Still, it remains unclear how active force generation contributes to its characteristic spindle-like shape. Here we combine theory and experiments to show that molecular motor-driven forces shape the structure through a barreling-type instability. We test our physical model by titrating dynein activity in Xenopus egg extract spindles and quantifying the shape and microtubule orientation. We conclude that spindles are shaped by the interplay between surface tension, nematic elasticity, and motor-driven active forces. Our study reveals how motor proteins can mold liquid crystalline droplets and has implications for the design of active soft materials.
@article{Oriola7713,
author={David Oriola, Frank Jülicher, Jan Brugués},
title={Active forces shape the metaphase spindle through a mechanical instability.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={117},
issue ={28},
pages={16154--16159},
year=2020
}