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Andreas Müller, Deborah Schmidt, C Shan Xu, Song Pang, Joyson Verner D'Costa, Susanne Kretschmar, Carla Münster, Thomas Kurth, Florian Jug, Martin Weigert, Harald Hess, Michele Solimena
3D FIB-SEM reconstruction of microtubule-organelle interaction in whole primary mouse β cells.
J Cell Biol, 220(2) Art. No. e202010039 (2021)
PubMed Source   

Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate. Here, we use FIB-SEM to image islet β cells in their entirety with unprecedented resolution. We reconstruct mitochondria, Golgi apparati, centrioles, insulin secretory granules, and microtubules of seven β cells, and generate a comprehensive spatial map of microtubule-organelle interactions. We find that microtubules form nonradial networks that are predominantly not connected to either centrioles or endomembranes. Microtubule number and length, but not microtubule polymer density, vary with glucose stimulation. Furthermore, insulin secretory granules are enriched near the plasma membrane, where they associate with microtubules. In summary, we provide the first 3D reconstructions of complete microtubule networks in primary mammalian cells together with evidence regarding their importance for insulin secretory granule positioning and thus their supportive role in insulin secretion.
@article{Müller7872,
author={Andreas Müller, Deborah Schmidt, C Shan Xu, Song Pang, Joyson Verner D'Costa, Susanne Kretschmar, Carla Münster, Thomas Kurth, Florian Jug, Martin Weigert, Harald Hess, Michele Solimena},
title={3D FIB-SEM reconstruction of microtubule-organelle interaction in whole primary mouse β cells.},
journal ={The Journal of cell biology},
volume={220},
issue ={2},
pages={1--1},
year=2021
}

Arnaud Rondelet, Andrei I. Pozniakovsky, Devika Namboodiri, Richard Cardoso da Silva, Divya Singh, Marit Leuschner, Ina Poser, Andrea Ssykor, Julian Berlitz, Nadine Schmidt, Lea Röhder, Gerben Vader, Anthony Hyman, Alexander W. Bird
ESI mutagenesis: a one-step method for introducing mutations into bacterial artificial chromosomes.
Life Sci Alliance, 4(2) Art. No. e202000836 (2021)
PubMed Source   

Bacterial artificial chromosome (BAC)-based transgenes have emerged as a powerful tool for controlled and conditional interrogation of protein function in higher eukaryotes. Although homologous recombination-based recombineering methods have streamlined the efficient integration of protein tags onto BAC transgenes, generating precise point mutations has remained less efficient and time-consuming. Here, we present a simplified method for inserting point mutations into BAC transgenes requiring a single recombineering step followed by antibiotic selection. This technique, which we call exogenous/synthetic intronization (ESI) mutagenesis, relies on co-integration of a mutation of interest along with a selectable marker gene, the latter of which is harboured in an artificial intron adjacent to the mutation site. Cell lines generated from ESI-mutated BACs express the transgenes equivalently to the endogenous gene, and all cells efficiently splice out the synthetic intron. Thus, ESI mutagenesis provides a robust and effective single-step method with high precision and high efficiency for mutating BAC transgenes.
@article{Rondelet7867,
author={Arnaud Rondelet, Andrei I. Pozniakovsky, Devika Namboodiri, Richard Cardoso da Silva, Divya Singh, Marit Leuschner, Ina Poser, Andrea Ssykor, Julian Berlitz, Nadine Schmidt, Lea Röhder, Gerben Vader, Anthony Hyman, Alexander W. Bird},
title={ESI mutagenesis: a one-step method for introducing mutations into bacterial artificial chromosomes.},
journal ={Life science alliance},
volume={4},
issue ={2},
pages={null--null},
year=2021
}

Sudarshan Gadadhar, Gonzalo Alvarez Viar, Jan Niklas Hansen, An Gong, Aleksandr Kostarev, Côme Ialy-Radio, Sophie Leboucher, Marjorie Whitfield, Ahmed Ziyyat, Aminata Touré, Luis Alvarez, Gaia Pigino, Carsten Janke
Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility.
Science, 371(6525) Art. No. eabd4914 (2021)
PubMed Source   

Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo-electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility.
@article{Gadadhar7878,
author={Sudarshan Gadadhar, Gonzalo Alvarez Viar, Jan Niklas Hansen, An Gong, Aleksandr Kostarev, Côme Ialy-Radio, Sophie Leboucher, Marjorie Whitfield, Ahmed Ziyyat, Aminata Touré, Luis Alvarez, Gaia Pigino, Carsten Janke},
title={Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility.},
journal ={Science (New York, N.Y.)},
volume={371},
issue ={6525},
pages={1--1},
year=2021
}

Karl Hoffmann, Ivo F. Sbalzarini
Robustness of topological defects in discrete domains
Phys Rev E, 103 Art. No. 012602 (2021)
  Source  

@article{Hoffmann7874,
author={Karl Hoffmann, Ivo F. Sbalzarini},
title={Robustness of topological defects in discrete domains},
journal ={Physical Review E},
volume={103},
pages={1--1},
year=2021
}

Kaushikaram Subramanian, Heike Petzold, Benjamin Seelbinder, Lena Herseman, Ina Nüsslein, Moritz Kreysing
Optical Plasticity of Mammalian Cells.
J Biophotonics, Art. No. doi: 10.1002/jbio.202000457 (2020)
PubMed Source   

Transparency is widespread in nature, ranging from transparent insect wings, to ocular tissues that enable you to read this text, and transparent marine vertebrates. And yet, cells and tissue models in biology are usually strongly light scattering and optically opaque, precluding deep optical microscopy. Here we describe the directed evolution of cultured mammalian cells towards increased transparency. We find that mutations greatly diversify the optical phenotype of Chinese Hamster Ovary cells, a cultured mammalian cell line. Furthermore, only 3 rounds of high-throughput optical selection and competitive growth are required to yield fit cells with greatly improved transparency. Based on 15 monoclonal cell lines derived from this directed evolution experiment, we find that the evolved transparency frequently goes along with a reduction of nuclear granularity and physiological shifts in gene expression profiles. In the future this optical plasticity of mammalian cells may facilitate genetic clearance of living tissues for in-vivo microscopy. This article is protected by copyright. All rights reserved.
@article{Subramanian7875,
author={Kaushikaram Subramanian, Heike Petzold, Benjamin Seelbinder, Lena Herseman, Ina Nüsslein, Moritz Kreysing},
title={Optical Plasticity of Mammalian Cells.},
journal ={Journal of biophotonics},
volume={},
pages={202000457--202000457},
year=2020
}

Anthony Hyman
ASCB Keith Porter Lecture.
Mol Biol Cell, 31(26) 2864-2867 (2020)
PubMed Source   

Although we attempt to plan the way we live, perhaps the best description of life is from the words of Yogi Berra: "It's tough to make predictions, especially about the future." A little over a year ago, I thought my future was predictable; after a fulfilling career, I would enjoy a last decade of research before a comfortable retirement. Then I lost my beloved wife and life partner, Suzanne Eaton to a senseless act of violence, and all assumptions were called into question.
@article{Hyman7870,
author={Anthony Hyman},
title={ASCB Keith Porter Lecture.},
journal ={Molecular biology of the cell},
volume={31},
issue ={26},
pages={2864--2867},
year=2020
}

Srija Bhagavatula, Elisabeth Knust
A putative stem-loop structure in Drosophila crumbs is required for mRNA localisation in epithelia and germline cells.
J Cell Sci, Art. No. doi: 10.1242/jcs.236497 (2020)
PubMed Source   

Crumbs (Crb) is an evolutionarily conserved transmembrane protein localised in the apical membrane of epithelial cells. Loss or mis-localisation of Crb is often associated with disruption of apico-basal cell polarity. crb mRNA is also apically enriched in epithelial cells, and, as shown here, accumulates in the oocyte of developing egg chambers. We narrowed down the Localization Element (LE) of crb mRNA to 47 nucleotides forming a putative stem-loop structure, suggesting to be recognised by Egalitarian (Egl). Mutations in conserved nucleotides abrogate apical transport. crb mRNA enrichment in the oocyte is affected in egl mutant egg chambers. A CRISPR based genomic deletion of the crb locus that includes the LE disrupts asymmetric crb mRNA localisation in epithelia and prevents its accumulation in the oocyte during early stages of oogenesis, but does not affect Crb protein localisation in embryonic and follicular epithelia. However, flies lacking the LE show ectopic Crb protein expression in the nurse cells. These data suggest an additional role of the Drosophila 3'-UTR in regulating translation in a tissue specific manner.
@article{Bhagavatula7871,
author={Srija Bhagavatula, Elisabeth Knust},
title={A putative stem-loop structure in Drosophila crumbs is required for mRNA localisation in epithelia and germline cells.},
journal ={Journal of cell science},
volume={},
pages={1--1},
year=2020
}

Louise Jawerth, Elisabeth Fischer-Friedrich, Suropriya Saha, Jie Wang, Titus Franzmann, Xiaojie Zhang, Jenny Sachweh, Martine Ruer, Mahdiye Ijavi, Shambaditya Saha, Julia Mahamid, Anthony Hyman, Frank Jülicher
Protein condensates as aging Maxwell fluids.
Science, 370(6522) 1317-1323 (2020)
PubMed Source   

Protein condensates are complex fluids that can change their material properties with time. However, an appropriate rheological description of these fluids remains missing. We characterize the time-dependent material properties of in vitro protein condensates using laser tweezer-based active and microbead-based passive rheology. For different proteins, the condensates behave at all ages as viscoelastic Maxwell fluids. Their viscosity strongly increases with age while their elastic modulus varies weakly. No significant differences in structure were seen by electron microscopy at early and late ages. We conclude that protein condensates can be soft glassy materials that we call Maxwell glasses with age-dependent material properties. We discuss possible advantages of glassy behavior for modulation of cellular biochemistry.
@article{Jawerth7866,
author={Louise Jawerth, Elisabeth Fischer-Friedrich, Suropriya Saha, Jie Wang, Titus Franzmann, Xiaojie Zhang, Jenny Sachweh, Martine Ruer, Mahdiye Ijavi, Shambaditya Saha, Julia Mahamid, Anthony Hyman, Frank Jülicher},
title={Protein condensates as aging Maxwell fluids.},
journal ={Science (New York, N.Y.)},
volume={370},
issue ={6522},
pages={1317--1323},
year=2020
}

Peiwen Xiong, C Darrin Hulsey, Carmelo Fruciano, Wai Y Wong, Alexander Nater, Andreas F Kautt, Oleg Simakov, Martin Pippel, Shigehiro Kuraku, Axel Meyer, Paolo Franchini
The comparative genomic landscape of adaptive radiation in crater lake cichlid fishes.
Mol. Ecol., Art. No. doi: 10.1111/mec.15774 (2020)
PubMed Source   

Factors ranging from ecological opportunity to genome composition might explain why only some lineages form adaptive radiations. While being rare, particular systems can provide natural experiments within an identical ecological setting where species numbers and phenotypic divergence in two closely related lineages are notably different. We investigated one such natural experiment using two de novo assembled and 40 resequenced genomes and asked why two closely related Neotropical cichlid fish lineages, the Amphilophus citrinellus species complex (Midas cichlids; radiating) and Archocentrus centrarchus (Flyer cichlid; nonradiating), have resulted in such disparate evolutionary outcomes. Although both lineages inhabit many of the same Nicaraguan lakes, whole-genome inferred demography suggests that priority effects are not likely to be the cause of the dissimilarities. Also, genome-wide levels of selection, transposable element dynamics, gene family expansion, major chromosomal rearrangements and the number of genes under positive selection were not markedly different between the two lineages. To more finely investigate particular subsets of the genome that have undergone adaptive divergence in Midas cichlids, we also examined if there was evidence for 'molecular pre-adaptation' in regions identified by QTL mapping of repeatedly diverging adaptive traits. Although most of our analyses failed to pinpoint substantial genomic differences, we did identify functional categories containing many genes under positive selection that provide candidates for future studies on the propensity of Midas cichlids to radiate. Our results point to a disproportionate role of local, rather than genome-wide factors underlying the propensity for these cichlid fishes to adaptively radiate.
@article{Xiong7879,
author={Peiwen Xiong, C Darrin Hulsey, Carmelo Fruciano, Wai Y Wong, Alexander Nater, Andreas F Kautt, Oleg Simakov, Martin Pippel, Shigehiro Kuraku, Axel Meyer, Paolo Franchini},
title={The comparative genomic landscape of adaptive radiation in crater lake cichlid fishes.},
journal ={Molecular ecology},
volume={},
pages={1--1},
year=2020
}

Tracy A Bedrosian, Judith Houtman, Juan Sebastian Eguiguren, Saeed Ghassemzadeh, N Rund, Nicole M Novaresi, Lauren Hu, Sarah L Parylak, Ahmet M Denli, Lynne Randolph-Moore, Takashi Namba, Fred H Gage, Tomohisa Toda
Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis.
EMBO J, Art. No. e105819 (2020)
PubMed Source   

Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age-dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age-related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age-related anxiety-like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation.
@article{Bedrosian7877,
author={Tracy A Bedrosian, Judith Houtman, Juan Sebastian Eguiguren, Saeed Ghassemzadeh, N Rund, Nicole M Novaresi, Lauren Hu, Sarah L Parylak, Ahmet M Denli, Lynne Randolph-Moore, Takashi Namba, Fred H Gage, Tomohisa Toda},
title={Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis.},
journal ={The EMBO journal},
volume={},
pages={null--null},
year=2020
}