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Isabel Ml Saur, Saskia Bauer, Barbara Kracher, Xunli Lu, Lamprinos Franzeskakis, Marion C Müller, Björn Sabelleck, Florian Kümmel, Ralph Panstruga, Takaki Maekawa, Paul Schulze-Lefert
Nucleotide-binding domain and leucine-rich repeat (NLR)-containing proteins in plants and animals mediate intracellular pathogen-sensing. Plant NLRs typically detect strain-specific pathogen effectors and trigger immune responses often linked to localized host cell death. The barley Mla disease resistance locus has undergone extensive functional diversification in the host population and encodes numerous allelic NLRs each detecting a matching isolate-specific avirulence effector (AVRA ) of the fungal pathogen Blumeria graminis f...
February 19, 2019: ELife
David M Kern, SeCheol Oh, Richard K Hite, Stephen Graf Brohawn
Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here we present single-particle cryo-electron microscopy structures of Mus musculus LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction...
February 18, 2019: ELife
Aminah T Ali, Lena Boehme, Guillermo Carbajosa, Vlad C Seitan, Kerrin S Small, Alan Hodgkinson
Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing >11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-encoded gene expression along the mitochondrial transcriptome, across tissues and between individuals, highlighting the importance of cell-type specific and post-transcriptional processes in shaping mitochondrial-encoded RNA levels...
February 18, 2019: ELife
Florent Campo-Paysaa, Jonathan Dw Clarke, Richard Jt Wingate
We use the transparency of zebrafish embryos to reveal the de novo generation of a simple squamous epithelium and identify the cellular architecture in the epithelial transition zone that ties this squamous epithelium to the columnar neuroepithelium within the embryo's brain. The simple squamous epithelium of the rhombencephalic roof plate is pioneered by distinct mesenchymal cells at the dorsal midline of the neural tube. Subsequently, a progenitor zone is established at the interface between columnar epithelium of the rhombic lip and the expanding squamous epithelium of the roof plate...
February 18, 2019: ELife
Felix Wong, Ethan C Garner, Ariel Amir
MreB is an actin homolog that is essential for coordinating the cell wall synthesis required for the rod shape of many bacteria. Previously we have shown that filaments of MreB bind to the curved membranes of bacteria and translocate in directions determined by principal membrane curvatures to create and reinforce the rod shape (Hussain et al., 2018). Here, in order to understand how MreB filament dynamics affects their cellular distribution, we model how MreB filaments bind and translocate on membranes with different geometries...
February 18, 2019: ELife
Alexey Shapiguzov, Julia P Vainonen, Kerri Hunter, Helena Tossavainen, Arjun Tiwari, Sari Järvi, Maarit Hellman, Fayezeh Aarabi, Saleh Alseekh, Brecht Wybouw, Katrien Van Der Kelen, Lauri Nikkanen, Julia Krasensky-Wrzaczek, Nina Sipari, Markku Keinänen, Esa Tyystjärvi, Eevi Rintamäki, Bert De Rybel, Jarkko Salojärvi, Frank van Breusegem, Alisdair R Fernie, Mikael Brosché, Perttu Permi, Eva-Mari Aro, Michael Wrzaczek, Jaakko Kangasjarvi
Reactive oxygen species (ROS)-dependent signaling pathways from chloroplasts and mitochondria merge at the nuclear protein RADICAL-INDUCED CELL DEATH1 (RCD1). RCD1 interacts in vivo and suppresses the activity of the transcription factors ANAC013 and ANAC017, which mediate a ROS-related retrograde signal originating from mitochondrial complex III. Inactivation of RCD1 leads to increased expression of mitochondrial dysfunction stimulon (MDS) genes regulated by ANAC013 and ANAC017. Accumulating MDS gene products, including alternative oxidases (AOXs), affect redox status of the chloroplasts, leading to changes in chloroplast ROS processing and increased protection of photosynthetic apparatus...
February 15, 2019: ELife
Li Fan, Ismar Kovacevic, Maxwell G Heiman, Zhirong Bao
Coordination of neurite morphogenesis with surrounding tissues is crucial to the establishment of neural circuits, but the underlying cellular and molecular mechanisms remain poorly understood. We show that neurons in a C. elegans sensory organ, called the amphid, undergo a collective dendrite extension to form the sensory nerve. The amphid neurons first assemble into a multicellular rosette. The vertex of the rosette, which becomes the dendrite tips, is attached to the anteriorly migrating epidermis and carried to the sensory depression, extruding the dendrites away from the neuronal cell bodies...
February 15, 2019: ELife
Thomas Aa Prowse, Fatwa Adikusuma, Phillip Cassey, Paul Thomas, Joshua V Ross
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that 'shreds' the Y chromosome, thereby converting XY males into fertile XO females...
February 15, 2019: ELife
Stephen M Hinshaw, Stephen C Harrison
Eukaryotic kinetochores connect spindle microtubules to chromosomal centromeres. A group of proteins called the Ctf19 complex (Ctf19c) in yeast and the constitutive centromere associated network (CCAN) in other organisms creates the foundation of a kinetochore. The Ctf19c/CCAN influences the timing of kinetochore assembly, sets its location by associating with a specialized nucleosome containing the histone H3 variant Cse4/CENP-A, and determines the organization of the microtubule attachment apparatus. We present here the structure of a reconstituted 13-subunit Ctf19c determined by cryo-electron microscopy at ~4 Å resolution...
February 14, 2019: ELife
Xue Yuan Pei, Tom Dendooven, Elisabeth Sonnleitner, Shaoxia Chen, Udo Blasi, Ben F Luisi
In diverse bacterial species, the global regulator Hfq contributes to post-transcriptional networks that control expression of numerous genes. Hfq of the opportunistic pathogen Pseudomonas aeruginosa inhibits translation of target transcripts by forming a regulatory complex with the catabolite repression protein Crc. This repressive complex acts part of an intricate mechanism of preferred nutrient utilisation. We describe high-resolution cryo-EM structures of the assembly of Hfq and Crc bound to the translation initiation site of a target mRNA...
February 13, 2019: ELife
Vikash Verma, Thomas Maresca
Microtubules (MTs) are essential for cleavage furrow positioning during cytokinesis, but the mechanisms by which MT-derived signals spatially define regions of cortical contractility are unresolved. In this study cytokinesis regulators visualized in Drosophila melanogaster ( Dm ) cells were found to localize to and track MT plus-ends during cytokinesis. The RhoA GEF Pebble ( Dm ECT2) did not evidently tip-track, but rather localized rapidly to cortical sites contacted by MT plus-tips, resulting in RhoA activation and enrichment of myosin-regulatory light chain...
February 13, 2019: ELife
L Bailey Lindenmaier, Nicolas Parmentier, Caiying Guo, Fadel Tissir, Kevin M Wright
Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the mammalian brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain...
February 13, 2019: ELife
Zhiling Li, Marlene M Hao, Chris Van den Haute, Veerle Baekelandt, Werend Boesmans, Pieter Vanden Berghe
The enteric nervous system controls a variety of gastrointestinal functions including intestinal motility. The minimal neuronal circuit necessary to direct peristalsis is well-characterized but several intestinal regions display also other motility patterns for which the underlying circuits and connectivity schemes that coordinate the transition between those patterns are poorly understood. We investigated whether in regions with a richer palette of motility patterns, the underlying nerve circuits reflect this complexity...
February 12, 2019: ELife
Shuo-Chien Ling, Somasish Ghosh Dastidar, Seiya Tokunaga, Wan Yun Ho, Kenneth Lim, Hristelina Ilieva, Philippe A Parone, Sheue-Houy Tyan, Tsemay M Tse, Jer-Cherng Chang, Oleksandr Platoshyn, Ngoc B Bui, Anh Bui, Anne Vetto, Shuying Sun, Melissa McAlonis-Downes, Joo Seok Han, Debbie Swing, Katannya Kapeli, Gene W Yeo, Lino Tessarollo, Martin Marsala, Christopher E Shaw, Greg Tucker-Kellogg, Albert R La Spada, Clotilde Lagier-Tourenne, Sandrine Da Cruz, Don W Cleveland
Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked mutants of human FUS in mice produces progressive motor phenotypes accompanied by characteristic ALS-like pathology. FUS levels are autoregulated by a mechanism in which human FUS downregulates endogenous FUS at mRNA and protein levels. Increasing wild-type human FUS expression achieved by saturating this autoregulatory mechanism produces a rapidly progressive phenotype and dose-dependent lethality...
February 12, 2019: ELife
Juan Pablo Alperin, Carol Muñoz Nieves, Lesley Schimanski, Gustavo E Fischman, Meredith T Niles, Erin C McKiernan
Much of the work done by faculty at both public and private universities has significant public dimensions: it is often paid for by public funds; it is often aimed at serving the public good; and it is often subject to public evaluation. To understand how the public dimensions of faculty work are valued, we analyzed review, promotion, and tenure documents from a representative sample of 129 universities in the US and Canada. Terms and concepts related to public and community are mentioned in a large portion of documents, but mostly in ways that relate to service, which is an undervalued aspect of academic careers...
February 12, 2019: ELife
Thomas Sebastian Benedikt Schmidt, Matthew Robert Hayward, Luis Pedro Coelho, Simone S Li, Paul Igor Costea, Anita Yvonne Voigt, Jakob Wirbel, Oleksandr M Maistrenko, Renato Jc Alves, Emma Bergsten, Carine de Beaufort, Iradj Sobhani, Anna Heintz-Buschart, Shinichi Sunagawa, Georg Zeller, Paul Wilmes, Peer Bork
The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens...
February 12, 2019: ELife
Wondwossen M Yeshaw, Marianne van der Zwaag, Francesco Pinto, Liza L Lahaye, Anita Ie Faber, Rubén Gómez-Sánchez, Amalia M Dolga, Conor Poland, Antony P Monaco, Sven van IJzendoorn, Nicola A Grzeschik, Antonio Velayos-Baeza, Ody Cm Sibon
The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact. VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. Interaction with mitochondria is mediated via its C-terminal domain...
February 11, 2019: ELife
Madhav Jagannathan, Ryan Cummings, Yukiko M Yamashita
A central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. Previously we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus (Jagannathan et al., 2018). Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a 'modular' network, where associations between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter...
February 11, 2019: ELife
Sam Li, Jose-Jesus Fernandez, Wallace F Marshall, David A Agard
Centriole is an essential structure with multiple functions in cellular processes. Centriole biogenesis and homeostasis is tightly regulated. Using electron cryo-tomography (cryoET) we present the structure of procentrioles from Chlamydomonas reinhardtii . We identified a set of non-tubulin components attached to the triplet microtubule (MT), many are at the junctions of tubules likely to reinforce the triplet. We describe structure of the A-C linker that bridges neighboring triplets. The structure infers that POC1 is likely an integral component of A-C linker...
February 11, 2019: ELife
Melissa Hebscher, Jed A Meltzer, Asaf Gilboa
Complex memory of personal events is thought to depend on coordinated reinstatement of cortical representations by the medial temporal lobes (MTL). MTL-cortical theta and gamma coupling is believed to mediate such coordination, but which cortical structures are critical for retrieval and how they influence oscillatory coupling is unclear. We used magnetoencephalography (MEG) combined with continuous theta burst stimulation (cTBS) to (i) clarify the roles of theta and gamma oscillations in network-wide communication during naturalistic memory retrieval, and (ii) understand the causal relationship between cortical network nodes and oscillatory communication...
February 11, 2019: ELife
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