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https://www.readbyqxmd.com/read/28817564/cell-cycle-related-kinase-ccrk-regulates-ciliogenesis-and-hedgehog-signaling-in-mice
#1
Ashley Snouffer, Desmond Brown, Hankyu Lee, Jonathon Walsh, Floria Lupu, Ryan Norman, Karl Lechtreck, Hyuk Wan Ko, Jonathan Eggenschwiler
The Hedgehog (Hh) signaling pathway plays a key role in cell fate specification, proliferation, and survival during mammalian development. Cells require a small organelle, the primary cilium, to respond properly to Hh signals and the key regulators of Hh signal transduction exhibit dynamic localization to this organelle when the pathway is activated. Here, we investigate the role of Cell Cycle Related kinase (CCRK) in regulation of cilium-dependent Hh signaling in the mouse. Mice mutant for Ccrk exhibit a variety of developmental defects indicative of inappropriate regulation of this pathway...
August 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28814779/the-beach-protein-lrba-promotes-the-localization-of-the-heterotrimeric-g-protein-golf-to-olfactory-cilia
#2
Stefan Kurtenbach, Andreas Gießl, Siv Strömberg, Jan Kremers, Jenny Atorf, Sebastian Rasche, Eva M Neuhaus, Denis Hervé, Johann Helmut Brandstätter, Esther Asan, Hanns Hatt, Manfred W Kilimann
BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA mutations cause severe immune deficiency. Here, we report a first functional and molecular phenotype outside the immune system of LRBA-knockout mice: compromised olfaction, manifesting in reduced electro-olfactogram response amplitude, impaired food-finding efficiency, and smaller olfactory bulbs...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814713/gelsolin-dysfunction-causes-photoreceptor-loss-in-induced-pluripotent-cell-and-animal-retinitis-pigmentosa-models
#3
Roly Megaw, Hashem Abu-Arafeh, Melissa Jungnickel, Carla Mellough, Christine Gurniak, Walter Witke, Wei Zhang, Hemant Khanna, Pleasantine Mill, Baljean Dhillon, Alan F Wright, Majlinda Lako, Charles Ffrench-Constant
Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments...
August 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28805871/asymmetric-motion-of-magnetically-actuated-artificial-cilia
#4
Srinivas Hanasoge, Matthew Ballard, Peter J Hesketh, Alexander Alexeev
Most microorganisms use hair-like cilia with asymmetric beating to perform vital bio-physical processes. In this paper, we demonstrate a novel fabrication method for creating magnetic artificial cilia capable of such a biologically inspired asymmetric beating pattern essential for inducing microfluidic transport at low Reynolds number. The cilia are fabricated using a lithographic process in conjunction with deposition of magnetic nickel-iron permalloy to create flexible filaments that can be manipulated by varying an external magnetic field...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28797107/jasplakinolide-induces-primary-cilium-formation-through-cell-rounding-and-yap-inactivation
#5
Tomoaki Nagai, Kensaku Mizuno
Primary cilia are non-motile cilia that serve as cellular antennae for sensing and transducing extracellular signals. In general, primary cilia are generated by cell quiescence signals. Recent studies have shown that manipulations to increase actin assembly suppress quiescence-induced ciliogenesis. To further examine the role of actin dynamics in ciliogenesis, we analyzed the effect of jasplakinolide (Jasp), a potent inducer of actin polymerization, on ciliogenesis. Unexpectedly, Jasp treatment induced ciliogenesis in serum-fed cells cultured at low density...
2017: PloS One
https://www.readbyqxmd.com/read/28775150/bcap-is-a-centriolar-satellite-protein-and-inhibitor-of-ciliogenesis
#6
Paul de Saram, Anila Iqbal, Jennifer N Murdoch, Christopher J Wilkinson
The centrosome and cilium are organelles with important roles in microtubule organisation, cell division, cell signalling, embryogenesis, and tissue homeostasis. The two organelles are mutually exclusive. The centriole/basal body is found at the core of the centrosome (centriole) or at the base of the cilium (basal body) and changing which organelle is present in a cell requires modification to the centriole/basal body both in terms of composition and sub-cellular localisation. While many protein components required for centrosome and cilium biogenesis have been described, there are far fewer known inhibitors of ciliogenesis...
August 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28760545/reactive-carbonyl-compounds-impair-wound-healing-by-vimentin-collapse-and-loss-of-the-primary-cilium
#7
Lara Rodríguez-Ribera, Craig Slattery, Tara Mc Morrow, Ricard Marcos, Susana Pastor
In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound-healing ability where the normal epithelial tissue is substituted for scar tissue caused by accumulation of extracellular matrix proteins (ECM). During the wound-healing process, epithelial cells may undergo epithelial-mesenchymal transition (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re-epithelialize the wound site. It has been reported that chronic inflammation and uremic milieu are involved in wound-healing and enhanced kidney damage in chronic kidney disease (CKD) patients...
July 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28754924/dynamic-scaffolds-for-neuronal-signaling-in-silico-analysis-of-the-tanc-protein-family
#8
Alessandra Gasparini, Silvio C E Tosatto, Alessandra Murgia, Emanuela Leonardi
The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scaffolds influencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743939/a-cryosectioning-technique-for-the-observation-of-intracellular-structures-and-immunocytochemistry-of-tissues-in-atomic-force-microscopy-afm
#9
Eiji Usukura, Akihiro Narita, Akira Yagi, Nobuaki Sakai, Yoshitsugu Uekusa, Yuka Imaoka, Shuichi Ito, Jiro Usukura
The use of cryosectioning facilitates the morphological analysis and immunocytochemistry of cells in tissues in atomic force microscopy (AFM). The cantilever can access all parts of a tissue sample in cryosections after the embedding medium (sucrose) has been replaced with phosphate-buffered saline (PBS), and this approach has enabled the production of a type of high-resolution image. The images resembled those obtained from freeze-etching replica electron microscopy (EM) rather than from thin-section EM. The AFM images showed disks stacked and enveloped by the cell membrane in rod photoreceptor outer segments (ROS) at EM resolution...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743734/centriole-translocation-and-degeneration-during-ciliogenesis-in-caenorhabditis-elegans-neurons
#10
Wenjing Li, Peishan Yi, Zhiwen Zhu, Xianliang Zhang, Wei Li, Guangshuo Ou
Neuronal cilia that are formed at the dendritic endings of sensory neurons are essential for sensory perception. However, it remains unclear how the centriole-derived basal body is positioned to form a template for cilium formation. Using fluorescence time-lapse microscopy, we show that the centriole translocates from the cell body to the dendrite tip in the Caenorhabditis elegans sensory neurons. The centriolar protein SAS-5 interacts with the dynein light-chain LC8 and conditional mutations of cytoplasmic dynein-1 block centriole translocation and ciliogenesis...
July 25, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28741966/the-connections-of-wnt-pathway-components-with-cell-cycle-and-centrosome-side-effects-or-a-hidden-logic
#11
Vítězslav Bryja, Igor Červenka, Lukáš Čajánek
Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division...
July 25, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28736169/protein-interaction-analysis-provides-a-map-of-the-spatial-and-temporal-organization-of-the-ciliary-gating-zone
#12
Daisuke Takao, Liang Wang, Allison Boss, Kristen J Verhey
The motility and signaling functions of the primary cilium require a unique protein and lipid composition that is determined by gating mechanisms localized at the base of the cilium. Several protein complexes localize to the gating zone and may regulate ciliary protein composition; however, the mechanisms of ciliary gating and the dynamics of the gating components are largely unknown. Here, we used the BiFC (bimolecular fluorescence complementation) assay and report for the first time on the protein-protein interactions that occur between ciliary gating components and transiting cargoes during ciliary entry...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28726664/expanded-phenotype-of-tmem67-gene-mutation-case-report
#13
T Tkemaladze, G Melikishvili, V Kherkheulidze, A Melikishvili, T Davitaia
Human ciliopathies are a class of multi-organ genetic disorders caused by defects of proteins expressed at the primary cilium, an organelle present on the cell surface of almost all cell types. Thus far, dozens of causative genes for ciliopathies have been identified and many of them are known to cause allelic disease. Of particular interest is the TMEM67 gene, encoding the transmembrane protein meckelin. The involvement of the mutant TMEM67 gene is known to be associated with a broad range of clinical presentations, namely Joubert syndrome 6 (JBTS6), nephronophthisis 11 (NPHP11), Bardet-Biedel syndrome (BBS), COACH syndrome, and lethal Meckel syndrome type 3 (MKS3)...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28724725/protein-diversity-in-discrete-structures-at-the-distal-tip-of-the-trypanosome-flagellum
#14
Vladimir Varga, Flavia Moreira-Leite, Neil Portman, Keith Gull
The distal end of the eukaryotic flagellum/cilium is important for axonemal growth and signaling and has distinct biomechanical properties. Specific flagellum tip structures exist, yet their composition, dynamics, and functions are largely unknown. We used biochemical approaches to identify seven constituents of the flagella connector at the tip of an assembling trypanosome flagellum and three constituents of the axonemal capping structure at the tips of both assembling and mature flagella. Both tip structures contain evolutionarily conserved as well as kinetoplastid-specific proteins, and component assembly into the structures occurs very early during flagellum extension...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28724397/partial-uniparental-isodisomy-of-chromosome-16-unmasks-a-deleterious-biallelic-mutation-in-ift140-that-causes-mainzer-saldino-syndrome
#15
Benjamin M Helm, Jason R Willer, Azita Sadeghpour, Christelle Golzio, Eric Crouch, Samantha Schrier Vergano, Nicholas Katsanis, Erica E Davis
BACKGROUND: The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings...
July 19, 2017: Human Genomics
https://www.readbyqxmd.com/read/28716465/fibroblast-like-synoviocyte-mechanosensitivity-to-fluid-shear-is-modulated-by-interleukin-1%C3%AE
#16
Eben G Estell, Lance A Murphy, Amy M Silverstein, Andrea R Tan, Roshan P Shah, Gerard A Ateshian, Clark T Hung
Fibroblast-like synoviocytes (FLS) reside in the synovial membrane of diarthrodial joints and are exposed to a dynamic fluid environment that presents both physical and chemical stimuli. The ability of FLS to sense and respond to these stimuli plays a key role in their normal function, and is implicated in the alterations to function that occur in osteoarthritis (OA). The present work characterizes the response of FLS to fluid flow-induced shear stress via real-time calcium imaging, and tests the hypothesis that this response is modulated by interleukin-1α (IL-1α), a cytokine elevated in OA...
June 28, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28710492/nek1-kinase-domain-structure-and-its-dynamic-protein-interactome-after-exposure-to-cisplatin
#17
Talita D Melo-Hanchuk, Priscila Ferreira Slepicka, Gabriela Vaz Meirelles, Fernanda Luisa Basei, Diogo Ventura Lovato, Daniela Campos Granato, Bianca Alves Pauletti, Romenia Ramos Domingues, Adriana Franco Paes Leme, Alessandra Luiza Pelegrini, Guido Lenz, Stefan Knapp, Jonathan M Elkins, Jörg Kobarg
NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710093/the-ciliary-membrane-associated-proteome-reveals-actin-binding-proteins-as-key-components-of-cilia
#18
Priyanka Kohli, Martin Höhne, Christian Jüngst, Sabine Bertsch, Lena K Ebert, Astrid C Schauss, Thomas Benzing, Markus M Rinschen, Bernhard Schermer
Primary cilia are sensory, antennae-like organelles present on the surface of many cell types. They have been involved in a variety of diseases collectively termed ciliopathies. As cilia are essential regulators of cell signaling, the composition of the ciliary membrane needs to be strictly regulated. To understand regulatory processes at the ciliary membrane, we report the targeting of a genetically engineered enzyme specifically to the ciliary membrane to allow biotinylation and identification of the membrane-associated proteome...
July 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28708866/a-new-index-for-characterizing-micro-bead-motion-in-a-flow-induced-by-ciliary-beating-part-ii-modeling
#19
Mathieu Bottier, Marta Peña Fernández, Gabriel Pelle, Daniel Isabey, Bruno Louis, James B Grotberg, Marcel Filoche
Mucociliary clearance is one of the major lines of defense of the human respiratory system. The mucus layer coating the airways is constantly moved along and out of the lung by the activity of motile cilia, expelling at the same time particles trapped in it. The efficiency of the cilia motion can experimentally be assessed by measuring the velocity of micro-beads traveling through the fluid surrounding the cilia. Here we present a mathematical model of the fluid flow and of the micro-beads motion. The coordinated movement of the ciliated edge is represented as a continuous envelope imposing a periodic moving velocity boundary condition on the surrounding fluid...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28706295/dgk%C3%AE-triggers-endoplasmic-reticulum-release-of-ift88-containing-vesicles-destined-for-the-assembly-of-primary-cilia
#20
Jie Ding, Lei Shao, Yixing Yao, Xin Tong, Huaize Liu, Shen Yue, Lu Xie, Steven Y Cheng
The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium, which relies on intraflagellar transport to maintain its structural integrity and function. However, the process by which protein and lipid cargos are delivered to the primary cilium from their sites of synthesis still remains poorly characterized. Here, we report that diacylglycerol kinase δ (DGKδ), a residential lipid kinase in the endoplasmic reticulum, triggers the release of IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth their movement to the primary cilium...
July 13, 2017: Scientific Reports
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