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https://www.readbyqxmd.com/read/28933593/dynein-promotes-porcine-oocyte-meiotic-progression-by-maintaining-cytoskeletal-structures-and-cortical-granule-arrangement
#1
Yilong Miao, Changyin Zhou, Zhaokang Cui, Liansheng Tang, Xiayan ShiYang, Yajuan Lu, Mianqun Zhang, Xiaoxin Dai, Bo Xiong
Cytoplasmic dynein is a family of cytoskeletal motor proteins that move towards the minus-end of the microtubules to perform functions in a variety of mitotic processes such as cargo transport, organelle positioning, chromosome movement and centrosome assembly. However, its specific roles during mammalian oocyte meiosis have not been fully defined. Herein, we investigated the critical events during porcine oocyte meiotic maturation after inhibition of dynein by Ciliobrevin D treatment. We found that oocyte meiotic progression was arrested when inhibited of dynein by showing the poor expansion of cumulus cells and decreased rate of polar body extrusion...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28931591/testing-the-time-of-flight-model-for-flagellar-length-sensing
#2
Hiroaki Ishikawa, Wallace F Marshall
Cilia and flagella are microtubule-based organelles that protrude from the surface of most cells, are important to sense extracellular signals and make a driving force for fluid flow. Maintenance of flagellar length requires an active transport process known as intraflagellar transport (IFT). Recent studies reveal that the amount of IFT injection negatively correlates with the length of flagella. These observations suggest that a length-dependent feedback regulates IFT. However, it is unknown how cells recognize the length of flagella and control IFT...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28930071/dynamics-of-the-ift-machinery-at-the-ciliary-tip
#3
Alexander Chien, Sheng Min Shih, Raqual Bower, Douglass Tritschler, Mary E Porter, Ahmet Yildiz
Intraflagellar transport (IFT) is essential for the elongation and maintenance of eukaryotic cilia and flagella. Due to the traffic jam of multiple trains at the ciliary tip, how IFT trains are remodeled in these turnaround zones cannot be determined by conventional imaging. Using Photogate, we visualized the full range of movement of single IFT trains and motors in Chlamydomonas flagella. Anterograde trains split apart and IFT complexes mix with each other at the tip to assemble retrograde trains. Dynein-1b is carried to the tip by kinesin-II as inactive cargo on anterograde trains...
September 20, 2017: ELife
https://www.readbyqxmd.com/read/28927820/a-novel-role-for-cilia-function-in-atopy-adgrv1-and-dnah5-interactions
#4
Pierre-Emmanuel Sugier, Myriam Brossard, Chloé Sarnowski, Amaury Vaysse, Andréanne Morin, Lucile Pain, Patricia Margaritte-Jeannin, Marie-Hélène Dizier, William O C M Cookson, Mark Lathrop, Miriam F Moffatt, Catherine Laprise, Florence Demenais, Emmanuelle Bouzigon
BACKGROUND: Atopy, an endotype underlying allergic diseases, has a substantial genetic component. OBJECTIVE: Our goal was to identify novel genes associated with atopy in asthma-ascertained families. METHODS: We implemented a three-step analysis strategy in three datasets: The Epidemiological study on the Genetics and Environment of Asthma (EGEA) dataset: 1,660 subjects; The Saguenay-Lac-Saint-Jean (SLSJ) dataset: 1,138 subjects; and The Medical Research Council (MRC) dataset: 446 subjects)...
September 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28923824/snapin-promotes-hiv-1-transmission-from-dendritic-cells-by-dampening-tlr8-signaling
#5
Elham Khatamzas, Madeleine Maria Hipp, Daniel Gaughan, Tica Pichulik, Alasdair Leslie, Ricardo A Fernandes, Daniele Muraro, Sarah Booth, Kieran Zausmer, Mei-Yi Sun, Benedikt Kessler, Sarah Rowland-Jones, Vincenzo Cerundolo, Alison Simmons
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4(+) T cells in DCs, including the dynein motor protein Snapin...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28922373/dynein-light-chain-regulates-adaptive-and-innate-b-cell-development-by-distinctive-genetic-mechanisms
#6
Ashleigh King, Lingli Li, David M Wong, Rui Liu, Rebecca Bamford, Andreas Strasser, David M Tarlinton, Jörg Heierhorst
Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, "natural" antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development...
September 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28915070/value-of-transmission-electron-microscopy-for-primary-ciliary-dyskinesia-diagnosis-in-the-era-of-molecular-medicine-genetic-defects-with-normal-and-non-diagnostic-ciliary-ultrastructure
#7
Adam J Shapiro, Margaret W Leigh
Primary ciliary dyskinesia (PCD) is a genetic disorder causing chronic oto-sino-pulmonary disease. No single diagnostic test will detect all PCD cases. Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic. These cases are identified through alternate diagnostic tests, including nasal nitric oxide measurement, high-speed videomicroscopy analysis, immunofluorescent staining of axonemal proteins, and/or mutation analysis of various PCD causing genes...
September 15, 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28910634/collaboration-between-distinct-rab-small-gtpase-trafficking-circuits-mediates-bacterial-clearance-from-the-bladder-epithelium
#8
Yuxuan Miao, Pradeep Bist, Jianxuan Wu, Qing Zhao, Qi-Jing Li, Ying Wan, Soman N Abraham
Rab small GTPases control membrane trafficking through effectors that recruit downstream mediators such as motor proteins. Subcellular trafficking typically involves multiple Rabs, with each specific step mediated by a distinct Rab protein. We describe a collaboration between two distinct Rab-protein-orchestrated trafficking circuits in bladder epithelial cells (BECs) that expels intracellular uropathogenic Escherichia coli (UPEC) from their intracellular niche. RAB11a and RAB27b and their trafficking circuitry are simultaneously involved in UPEC expulsion...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28901718/chondroitin-sulfate-proteoglycans-negatively-regulate-the-positioning-of-mitochondria-and-endoplasmic-reticulum-to-distal-axons
#9
Rajiv Sainath, Lorena Armijo-Weingart, Andrea Ketscheck, Zhuxuan Xu, Shuxin Li, Gianluca Gallo
Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix that inhibit the extension and regeneration of axons. However, the underlying mechanism of action remains poorly understood. Mitochondria and endoplasmic reticulum (ER) are functionally inter-linked organelles important to axon development and maintenance. We report that CSPGs impair the targeting of mitochondria and ER to the growth cones of chicken embryonic sensory axons. The effect of CSPGs on the targeting of mitochondria is blocked by inhibition of the LAR receptor for CSPGs...
September 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28901373/kinesin-and-dynein-mechanics-measurement-methods-and-research-applications
#10
Zachary Abraham, Emma Hawley, Daniel Hayosh, Victoria Webster-Wood, Ozan Akkus
Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two types of proteins, kinesin and dynein, have been shown to lead many pathologies, including neurodegenerative diseases and cancers. As such, it is critical for researchers to understand the underlying mechanics and behaviors of these proteins, not only to shed light on how failures may lead to disease, but also to guide research towards novel treatment and nanoengineering solutions...
September 13, 2017: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/28899926/peptides-mediating-dna-transport-on-microtubules-and-their-impact-on-non-viral-gene-transfer-efficiency
#11
Patrick Midoux, Lucie Pigeon, Cristine Gonçalves, Chantal Pichon
Synthetic vectors such as cationic polymers and cationic lipids remain attractive tools for non-viral gene transfer which is a complex process whose effectiveness relies on the ability to deliver a plasmid DNA (pDNA) into the nucleus of non-dividing cells. Once in the cytosol, the transport of pDNAs towards the nuclear envelop is strongly impaired by their very low cytosolic mobility due to their large size. To promote their movement towards the cell nucleus, few strategies have been implemented to exploit dynein, the microtubule's motor protein, for propagation of cytosolic pDNA along the microtubules (MTs) towards the cell nucleus...
September 12, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28892495/chlamydomonas-dyx1c1-pf23-is-essential-for-axonemal-assembly-and-proper-morphology-of-inner-dynein-arms
#12
Ryosuke Yamamoto, Jagan M Obbineni, Lea M Alford, Takahiro Ide, Mikito Owa, Juyeon Hwang, Takahide Kon, Kazuo Inaba, Noliyanda James, Stephen M King, Takashi Ishikawa, Winfield S Sale, Susan K Dutcher
Cytoplasmic assembly of ciliary dyneins, a process known as preassembly, requires numerous non-dynein proteins, but the identities and functions of these proteins are not fully elucidated. Here, we show that the classical Chlamydomonas motility mutant pf23 is defective in the Chlamydomonas homolog of DYX1C1. The pf23 mutant has a 494 bp deletion in the DYX1C1 gene and expresses a shorter DYX1C1 protein in the cytoplasm. Structural analyses, using cryo-ET, reveal that pf23 axonemes lack most of the inner dynein arms...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28892477/allosteric-conformational-change-cascade-in-cytoplasmic-dynein-revealed-by-structure-based-molecular-simulations
#13
Shintaroh Kubo, Wenfei Li, Shoji Takada
Cytoplasmic dynein is a giant ATP-driven molecular motor that proceeds to the minus end of the microtubule (MT). Dynein hydrolyzes ATP in a ring-like structure, containing 6 AAA+ (ATPases associated with diverse cellular activities) modules, which is ~15 nm away from the MT binding domain (MTBD). This architecture implies that long-distance allosteric couplings exist between the AAA+ ring and the MTBD in order for dynein to move on the MT, although little is known about the mechanisms involved. Here, we have performed comprehensive molecular simulations of the dynein motor domain based on pre- and post- power-stroke structural information and in doing so we address the allosteric conformational changes that occur during the power-stroke and recovery-stroke processes...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28886386/lis1-has-two-opposing-modes-of-regulating-cytoplasmic-dynein
#14
Morgan E DeSantis, Michael A Cianfrocco, Zaw Min Htet, Phuoc Tien Tran, Samara L Reck-Peterson, Andres E Leschziner
Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here-a combination of biochemistry, single-molecule assays, and cryoelectron microscopy-led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28883641/calaxin-establishes-basal-body-orientation-and-coordinates-movement-of-monocilia-in-sea-urchin-embryos
#15
Katsutoshi Mizuno, Kogiku Shiba, Junko Yaguchi, Daisuke Shibata, Shunsuke Yaguchi, Gérard Prulière, Janet Chenevert, Kazuo Inaba
Through their coordinated alignment and beating, motile cilia generate directional fluid flow and organismal movement. While the mechanisms used by multiciliated epithelial tissues to achieve this coordination have been widely studied, much less is known about regulation of monociliated tissues such as those found in the vertebrate node and swimming planktonic larvae. Here, we show that a calcium sensor protein associated with outer arm dynein, calaxin, is a critical regulator for the coordinated movements of monocilia...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883039/disease-associated-mutations-in-human-bicd2-hyperactivate-motility-of-dynein-dynactin
#16
Walter Huynh, Ronald D Vale
Bicaudal D2 (BICD2) joins dynein with dynactin into a ternary complex (termed DDB) capable of processive movement. Point mutations in the BICD2 gene have been identified in patients with a dominant form of spinal muscular atrophy, but how these mutations cause disease is unknown. To investigate this question, we have developed in vitro motility assays with purified DDB and BICD2's membrane vesicle partner, the GTPase Rab6a. Rab6a-GTP, either in solution or bound to artificial liposomes, released BICD2 from an autoinhibited state and promoted robust dynein-dynactin transport...
September 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28875937/notch-her12-signalling-modulates-motile-immotile-cilia-ratio-downstream-of-foxj1a-in-zebrafish-left-right-organizer
#17
Barbara Tavares, Raquel Jacinto, Pedro Sampaio, Sara Pestana, Andreia Pinto, Andreia Vaz, Mónica Roxo-Rosa, Rui Gardner, Telma Lopes, Britta Schilling, Ian Henry, Leonor Saúde, Susana Santos Lopes
Foxj1a is necessary and sufficient to specify motile cilia. Using transcriptional studies and slow-scan two-photon live imaging capable of identifying the number of motile and immotile cilia, we now established that the final number of motile cilia depends on Notch signalling (NS). We found that despite all left-right organizer (LRO) cells express foxj1a and the ciliary axonemes of these cells have dynein arms some cilia remain immotile. We identified that this decision is taken early in development in the Kupffer's Vesicle (KV) precursors the readout being her12 transcription...
September 5, 2017: ELife
https://www.readbyqxmd.com/read/28870165/myosin-repertoire-expansion-coincides-with-eukaryotic-diversification-in-the-mesoproterozoic-era
#18
Martin Kollmar, Stefanie Mühlhausen
BACKGROUND: The last eukaryotic common ancestor already had an amazingly complex cell possessing genomic and cellular features such as spliceosomal introns, mitochondria, cilia-dependent motility, and a cytoskeleton together with several intracellular transport systems. In contrast to the microtubule-based dyneins and kinesins, the actin-filament associated myosins are considerably divergent in extant eukaryotes and a unifying picture of their evolution has not yet emerged. RESULTS: Here, we manually assembled and annotated 7852 myosins from 929 eukaryotes providing an unprecedented dense sequence and taxonomic sampling...
September 4, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28864767/sequential-activities-of-dynein-mud-and-asp-in-centrosome-spindle-coupling-maintain-centrosome-number-upon-mitosis
#19
Floris Bosveld, Anna Ainslie, Yohanns Bellaïche
Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known on the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in Drosophila) is best known for its role in spindle orientation. Here we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in Drosophila epithelial cells...
September 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28858830/exposure-to-low-levels-of-lead-in-utero-and-umbilical-cord-blood-dna-methylation-in-project-viva-an-epigenome-wide-association-study
#20
Shaowei Wu, Marie-France Hivert, Andres Cardenas, Jia Zhong, Sheryl L Rifas-Shiman, Golareh Agha, Elena Colicino, Allan C Just, Chitra Amarasiriwardena, Xihong Lin, Augusto A Litonjua, Dawn L DeMeo, Matthew W Gillman, Robert O Wright, Emily Oken, Andrea A Baccarelli
BACKGROUND: Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. OBJECTIVES: We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U...
August 25, 2017: Environmental Health Perspectives
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