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Dynein

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https://www.readbyqxmd.com/read/28533393/angular-measurements-of-the-dynein-ring-reveal-a-stepping-mechanism-dependent-on-a-flexible-stalk
#1
Lisa G Lippert, Tali Dadosh, Jodi A Hadden, Vishakha Karnawat, Benjamin T Diroll, Christopher B Murray, Erika L F Holzbaur, Klaus Schulten, Samara L Reck-Peterson, Yale E Goldman
The force-generating mechanism of dynein differs from the force-generating mechanisms of other cytoskeletal motors. To examine the structural dynamics of dynein's stepping mechanism in real time, we used polarized total internal reflection fluorescence microscopy with nanometer accuracy localization to track the orientation and position of single motors. By measuring the polarized emission of individual quantum nanorods coupled to the dynein ring, we determined the angular position of the ring and found that it rotates relative to the microtubule (MT) while walking...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28524820/chemical-structure-guided-design-of-dynapyrazoles-potent-cell-permeable-dynein-inhibitors-with-a-unique-mode-of-action
#2
Jonathan Baruch Steinman, Cristina C Santarossa, Rand M Miller, Lola S Yu, Anna S Serpinskaya, Hideki Furukawa, Sachie Morimoto, Yuta Tanaka, Mitsuyoshi Nishitani, Moriteru Asano, Ruta Zalyte, Alison E Ondrus, Alex G Johnson, Fan Ye, Maxence V Nachury, Yoshiyuki Fukase, Kazuyoshi Aso, Michael A Foley, Vladimir I Gelfand, James K Chen, Andrew P Carter, Tarun M Kapoor
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that power transport of cellular cargos towards microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally-constrained isosteres...
May 19, 2017: ELife
https://www.readbyqxmd.com/read/28515232/the-nuclear-export-factor-crm1-controls-juxta-nuclear-microtubule-dependent-virus-transport
#3
I-Hsuan Wang, Christoph J Burckhardt, Artur Yakimovich, Matthias K Morf, Urs F Greber
Transport of large cargo through the cytoplasm requires motor proteins and polarized filaments. Viruses that replicate in the nucleus of post-mitotic cells use microtubules and the dynein/dynactin motor to traffic to the nuclear membrane, and deliver their genome through nuclear pore complexes (NPCs) into the nucleus. How virus particles (virions) or cellular cargo are transferred from microtubules to the NPC is unknown. Here, we analyzed trafficking of incoming cytoplasmic adenoviruses by single particle tracking and super-resolution microscopy...
May 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28513584/kinesin-5-independent-mitotic-spindle-assembly-requires-the-antiparallel-microtubule-crosslinker-ase1-in-fission-yeast
#4
Sergio A Rincon, Adam Lamson, Robert Blackwell, Viktoriya Syrovatkina, Vincent Fraisier, Anne Paoletti, Meredith D Betterton, Phong T Tran
Bipolar spindle assembly requires a balance of forces where kinesin-5 produces outward pushing forces to antagonize the inward pulling forces from kinesin-14 or dynein. Accordingly, Kinesin-5 inactivation results in force imbalance leading to monopolar spindle and chromosome segregation failure. In fission yeast, force balance is restored when both kinesin-5 Cut7 and kinesin-14 Pkl1 are deleted, restoring spindle bipolarity. Here we show that the cut7Δpkl1Δ spindle is fully competent for chromosome segregation independently of motor activity, except for kinesin-6 Klp9, which is required for anaphase spindle elongation...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28500304/microgravity-induces-inhibition-of-osteoblastic-differentiation-and-mineralization-through-abrogating-primary-cilia
#5
Wengui Shi, Yanfang Xie, Jinpeng He, Jian Zhou, Yuhai Gao, Wenjun Wei, Nan Ding, Huiping Ma, Cory J Xian, Keming Chen, Jufang Wang
It is well documented that microgravity in space environment leads to bone loss in astronauts. These physiological changes have also been validated by human and animal studies and modeled in cell-based analogs. However, the underlying mechanisms are elusive. In the current study, we identified a novel phenomenon that primary cilia (key sensors and functioning organelles) of rat calvarial osteoblasts (ROBs) gradually shrank and disappeared almost completely after exposure to simulated microgravity generated by a random positioning machine (RPM)...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28496122/structural-insights-into-a-20-8-kda-tegumental-allergen-like-tal-protein-from-clonorchis-sinensis
#6
Chang Hwa Jo, Jonghyeon Son, Sulhee Kim, Takashi Oda, Jaehoon Kim, Myoung-Ro Lee, Mamoru Sato, Hyun Tae Kim, Satoru Unzai, Sam-Yong Park, Kwang Yeon Hwang
Survival of Clonorchis sinensis, a cause of human clonorchiasis, requires tegument proteins, which are localized to the tegumental outer surface membrane. These proteins play an important role in a host response and parasite survival. Thus, these proteins are interesting molecular targets for vaccine and drug development. Here, we have determined two crystal structures of the calmodulin like domain (amino acid [aa] positions 1-81) and dynein light chain (DLC)-like domain (aa 83-177) of a 20.8-kDa tegumental-allergen-like protein from Clonorchis sinensis (CsTAL3)...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494707/histologic-and-ultrastructural-findings-in-dogs-with-chronic-respiratory-disease-suspected-of-ciliary-dyskinesia
#7
Ileana C Miranda, Jennifer L Granick, Anibal G Armién
Mucociliary clearance is a main defense mechanism of the respiratory tract, which can be inherently impaired in primary ciliary dyskinesia (PCD) or reversibly altered in secondary ciliary dyskinesia (SCD). Limited diagnostic test availability likely leads to misdiagnosis or underdiagnosis of PCD in animals. This study evaluated the light and transmission electron microscopy (TEM) changes in the respiratory mucosa of 15 dogs with chronic respiratory disease suspected of PCD. Necropsy was performed in 1 case and 2 dogs were used as negative controls...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28490590/the-c-terminus-of-the-herpes-simplex-virus-pul25-protein-is-required-for-release-of-viral-genomes-from-capsids-bound-to-nuclear-pores
#8
Jamie B Huffman, Gina R Daniel, Erik Falck-Pedersen, Alexis Huet, Greg A Smith, James F Conway, Fred L Homa
The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion of viral and host membranes, whereupon dynein-dependent trafficking along microtubules targets it to the nuclear envelope. Binding of the capsid to the nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid-tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been difficult to study due to the rapid release of the genome once the capsid interacts with the nuclear pore...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28479887/long-term-outcome-of-tunisian-children-with-primary-ciliary-dyskinesia-confirmed-by-transmission-electron-microscopy
#9
Hamouda Samia, Boussetta Khadija, Hamzaoui Agnes, Khalsi Fatma, Trabelsi Ines, Jaafoura Hafedh, Tinsa Faten
BACKGROUND: Primary ciliary dyskinesia (PCD) is rare. Its diagnosis requires experienced specialists and expensive infrastructure. Its prognosis is variable. OBJECTIVE: To study the long-term outcome of PCD in Tunisian children with ciliary ultra-structure defects detected by electron microscope. METHODS: Covering a period of 20 years (1996-2015), this retrospective study included all patients with definite PCD (outer dynein arms (DA) defects and/or situs inversus) and presumed PCD (other ciliary ultra-structure defects)...
December 2016: African Health Sciences
https://www.readbyqxmd.com/read/28479320/dynein-driven-retrograde-intraflagellar-transport-is-triphasic-in-c-%C3%A2-elegans-sensory-cilia
#10
Peishan Yi, Wen-Jun Li, Meng-Qiu Dong, Guangshuo Ou
Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance. Inactivation of dynein-2 by mutations in DYNC2H1 causes skeletal dysplasias, and it remains unclear how the dynein-2 heavy chain moves in cilia. Here, using the genome-editing technique to produce fluorescent dynein-2 heavy chain in Caenorhabditis elegans, we show by high-resolution live microscopy that dynein-2 moves in a surprising way along distinct ciliary domains. Dynein-2 shows triphasic movement in the retrograde direction: dynein-2 accelerates in the ciliary distal region and then moves at maximum velocity and finally decelerates adjacent to the base, which may represent a physical obstacle due to transition zone barriers...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28477148/a-low-ca-2-i-induced-enhancement-of-camp-activated-ciliary-beating-by-pde1a-inhibition-in-mouse-airway-cilia
#11
Haruka Kogiso, Shigekuni Hosogi, Yukiko Ikeuchi, Saori Tanaka, Chikao Shimamoto, Hitoshi Matsumura, Takashi Nakano, Koh-Ichi Sano, Toshio Inui, Yoshinori Marunaka, Takashi Nakahari
This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an β2-agonist) increased the ciliary bend angle (CBA) and CBF via cAMP accumulation in the ciliary cells of mice: interestingly, the time course of CBF increase was slower than that of CBA increase. However, IBMX (3-isobutyl-1-methylxanthine, an inhibitor of PDE) increased CBA and CBF in an identical time course...
May 5, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28472620/bidirectionality-from-cargo-thermal-fluctuations-in-motor-mediated-transport
#12
Christopher E Miles, James P Keener
Molecular motor proteins serve as an essential component of intracellular transport by generating forces to haul cargoes along cytoskeletal filaments. Two species of motors that are directed oppositely (e.g. kinesin, dynein) can be attached to the same cargo, which is known to produce bidirectional net motion. Although previous work focuses on the motor number as the driving noise source for switching, we propose an alternative mechanism: cargo diffusion. A mean-field mathematical model of mechanical interactions of two populations of molecular motors with cargo thermal fluctuations (diffusion) is presented to study this phenomenon...
May 1, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28468979/increased-lateral-microtubule-contact-at-the-cell-cortex-is-sufficient-to-drive-mammalian-spindle-elongation
#13
Joshua Guild, Miriam B Ginzberg, Christina L Hueschen, Timothy J Mitchison, Sophie Dumont
The spindle is a dynamic structure that changes its architecture and size in response to biochemical and physical cues. For example, a simple physical change, cell confinement, can trigger centrosome separation and increase spindle steady-state length at metaphase. How this occurs is not understood, and is the question we pose here. We find that metaphase and anaphase spindles elongate at the same rate when confined, suggesting that similar elongation forces can be generated independent of biochemical and spindle structural differences...
May 3, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28461574/microtubule-based-transport-and-the-distribution-tethering-and-organization-of-organelles
#14
REVIEW
Kari Barlan, Vladimir I Gelfand
SUMMARYMicrotubules provide long tracks along which a broad range of organelles and vesicles are transported by kinesin and dynein motors. Motor protein complexes also tether cargoes to cytoskeletal filaments, helping facilitate their interaction and communication. The generation of biochemically distinct microtubule subpopulations allows subsets of motors to recognize a given microtubule identity, allowing further organization within the cytoplasm. Both transport and tethering are spatiotemporally regulated through multiple modes, including acute modification of both motor-cargo and motor-track associations by various physiological signals...
May 1, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28455235/computational-prediction-and-analysis-of-deleterious-cancer-associated-missense-mutations-in-dync1h1
#15
Ceren Sucularli, Melda Arslantas
Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene encodes a subunit of human cytoplasmic dynein complex, which has several crucial functions in the cell, such as intracellular transport of DNA damage proteins and mitotic spindle positioning. Recent studies reported the altered expression of DYNC1H1 in different cancers and DYNC1H1 was suggested to be potential biomarker in colorectal cancers. Previously, DYNC1H1 mutations have been associated with neurodegenerative diseases, however mutations of DYNC1H1 have not been fully investigated in cancers except for different types of pancreatic cancers...
April 25, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28442535/multiple-kinesin-14-family-members-drive-microtubule-minus-end-directed-transport-in-plant-cells
#16
Moé Yamada, Yohko Tanaka-Takiguchi, Masahito Hayashi, Momoko Nishina, Gohta Goshima
Minus end-directed cargo transport along microtubules (MTs) is exclusively driven by the molecular motor dynein in a wide variety of cell types. Interestingly, during evolution, plants have lost the genes encoding dynein; the MT motors that compensate for dynein function are unknown. Here, we show that two members of the kinesin-14 family drive minus end-directed transport in plants. Gene knockout analyses of the moss Physcomitrella patens revealed that the plant-specific class VI kinesin-14, KCBP, is required for minus end-directed transport of the nucleus and chloroplasts...
April 25, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28441108/novel-clades-of-the-hu-ihf-superfamily-point-to-unexpected-roles-in-the-eukaryotic-centrosome-chromosome-partitioning-and-biologic-conflicts
#17
A Maxwell Burroughs, Gurmeet Kaur, Dapeng Zhang, L Aravind
The HU superfamily of proteins, with a unique DNA-binding mode, has been extensively studied as the primary chromosome-packaging protein of the bacterial superkingdom. Representatives also play a role in DNA-structuring during recombination events and in eukaryotic organellar genome maintenance. However, beyond these well-studied roles, little is understood of the functional diversification of this large superfamily. Using sensitive sequence and structure analysis methods we identify multiple novel clades of the HU superfamily...
April 25, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28432079/regulation-of-microtubule-associated-motors-drives-intermediate-filament-network-polarization
#18
Cécile Leduc, Sandrine Etienne-Manneville
Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28427147/brca1-controls-the-cell-division-axis-and-governs-ploidy-and-phenotype-in-human-mammary-cells
#19
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424932/inverse-relationship-of-ca-2-dependent-flagellar-response-between-animal-sperm-and-prasinophyte-algae
#20
Kogiku Shiba, Kazuo Inaba
Symmetry/asymmetry conversion of eukaryotic flagellar waveform is caused by the changes in intracellular Ca(2+). Animal sperm flagella show symmetric or asymmetric waveform at lower or higher concentration of intracellular Ca(2+), respectively. In Chlamydomonas, high Ca(2+) induces conversion of flagellar waveform from asymmetric to symmetry, resulting in the backward movement. This mirror image relationship between animal sperm and Chlamydomonas could be explained by the distinct calcium sensors used to regulate the outer arm dyneins (Inaba 2015)...
April 19, 2017: Journal of Plant Research
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