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https://www.readbyqxmd.com/read/28445929/the-kinesin-motor-protein-kif7-is-required-for-t-cell-development-and-normal-mhc-expression-on-thymic-epithelial-cells-tec-in-the-thymus
#1
Ching-In Lau, Alessandro Barbarulo, Anisha Solanki, José Ignacio Saldaña, Tessa Crompton
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444394/tissue-specific-dissociation-of-diurnal-transcriptome-rhythms-during-sleep-restriction-in-mice
#2
Jana Husse, Jana-Thabea Kiehn, Johanna L Barclay, Nadine Naujokat, Judit Meyer-Kovac, Hendrik Lehnert, Henrik Oster
Study objectives: Shortened or mistimed sleep affects metabolic homeostasis, which may in part be mediated by dysregulation of endogenous circadian clocks. In this study, we assessed the contribution of sleep disruption to metabolic dysregulation by analysing diurnal transcriptome regulation in metabolic tissues of mice subjected to a sleep restriction paradigm. Methods: Male mice were subjected to 2x5 days of sleep restriction (SR) with enforced waking during the first six hours of the light phase...
April 24, 2017: Sleep
https://www.readbyqxmd.com/read/28442542/missense-mutations-in-the-wd40-domain-of-ahi1-cause-non-syndromic-retinitis-pigmentosa
#3
Thanh-Minh T Nguyen, Sarah Hull, Ronald Roepman, L Ingeborgh van den Born, Machteld M Oud, Erik de Vrieze, Lisette Hetterschijt, Stef J F Letteboer, Sylvia E C van Beersum, Ellen A Blokland, Helger G Yntema, Frans P M Cremers, Paul A van der Zwaag, Gavin Arno, Erwin van Wijk, Andrew R Webster, Lonneke Haer-Wigman
BACKGROUND: Recent findings suggesting that Abelson helper integration site 1 (AHI1) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). METHODS: Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling...
April 25, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28441853/-differentially-expressed-genes-analysis-in-expression-profile-data-of-pulmonary-fibrosis-with-pulmonary-hypertension
#4
R Miao, D Leng, Y Wang, J F Li, J N Gong, Y Liang, Y H Yang
Objective: To analyze the differential gene expression of patients with idiopathic pulmonary fibrosis and pulmonary hypertension (IPF-PH). Methods: The expression profile data of GSE15197 was downloaded from the Gene Expression Omnibus (GEO) database. Bonferroni algorithm was used to identify the differentially expressed genes of pulmonary tissues from IPF-PH, idiopathic pulmonary arterial hypertension (IPAH) and Normal groups. Principal component analysis was used to extract the principal components of three types of samples and differentially expressed genes were obtained...
April 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28432921/gates-for-soluble-and-membrane-proteins-and-two-trafficking-systems-ift-and-lift-establish-a-dynamic-ciliary-signaling-compartment
#5
REVIEW
Victor L Jensen, Michel R Leroux
Primary cilia are microtubule-based organelles found on most mammalian cell surfaces. They possess a soluble matrix and membrane contiguous with the cell body cytosol and plasma membrane, and yet, have distinct compositions that can be modulated to enable dynamic signal transduction. Here, we discuss how specialized ciliary compartments are established using a coordinated network of gating, trafficking and targeting activities. Cilium homeostasis is maintained by a size-selective molecular mesh that limits soluble protein entry, and by a membrane diffusion barrier localized at the transition zone...
April 19, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28432464/insights-into-autosomal-dominant-polycystic-kidney-disease-by-quantitative-mass-spectrometry-based-proteomics
#6
REVIEW
Britta Diedrich, Jörn Dengjel
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PKD1 and PKD2 encoding polycystin-1 and polycystin-2, respectively. Polycystin-1 and -2 form a complex, interact with several proteins involved in signal transduction and localize to discrete subcellular positions, most importantly the primary cilium. Whereas the causative mutations leading to ADPKD are known, the underlying deregulated cellular pathways are not well understood. In the current review, we introduce state-of-the-art mass spectrometry (MS)-based proteomic techniques and summarize their use in kidney and ADPKD research...
April 21, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28411364/centriolar-remodeling-underlies-basal-body-maturation-during-ciliogenesis-in-caenorhabditis-elegans
#7
Inna V Nechipurenko, Cristina Berciu, Piali Sengupta, Daniela Nicastro
The primary cilium is nucleated by the mother centriole-derived basal body (BB) via as yet poorly characterized mechanisms. BBs have been reported to degenerate following ciliogenesis in the C. elegans embryo, although neither BB architecture nor early ciliogenesis steps have been described in this organism. In a previous study (Doroquez et al., 2014), we described the three-dimensional morphologies of sensory neuron cilia in adult C. elegans hermaphrodites at high resolution. Here, we use serial section electron microscopy and tomography of staged C...
April 15, 2017: ELife
https://www.readbyqxmd.com/read/28411024/epcam-controls-morphogenetic-programs-during-zebrafish-pronephros-development
#8
Sebastian Kuechlin, Maximilian Schoels, Krasimir Slanchev, Silke Lassmann, Gerd Walz, Toma A Yakulov
Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is dynamically expressed in human and murine renal epithelia during development. The levels of EpCAM in the renal epithelium are upregulated both during regeneration after ischemia/reperfusion injury and in renal-derived carcinomas. The role of EpCAM in early kidney development, however, has remained unclear. The zebrafish pronephros shows a similar segmentation pattern to the mammalian metanephric nephron, and has recently emerged as a tractable model to study the regulatory programs governing early nephrogenesis...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28409350/primary-cilia-in-cystic-kidney-disease
#9
Prachee Avasthi, Robin L Maser, Pamela V Tran
Primary cilia are small, antenna-like structures that detect mechanical and chemical cues and transduce extracellular signals. While mammalian primary cilia were first reported in the late 1800s, scientific interest in these sensory organelles has burgeoned since the beginning of the twenty-first century with recognition that primary cilia are essential to human health. Among the most common clinical manifestations of ciliary dysfunction are renal cysts. The molecular mechanisms underlying renal cystogenesis are complex, involving multiple aberrant cellular processes and signaling pathways, while initiating molecular events remain undefined...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28405397/dynamics-of-cilia-length-in-left-right-development
#10
P Pintado, P Sampaio, B Tavares, T D Montenegro-Johnson, D J Smith, S S Lopes
Reduction in the length of motile cilia in the zebrafish left-right organizer (LRO), also known as Kupffer's vesicle, has a large impact on left-right development. Here we demonstrate through genetic overexpression in zebrafish embryos and mathematical modelling that the impact of increased motile cilia length in embryonic LRO fluid flow is milder than that of short cilia. Through Arl13b overexpression, which increases cilia length without impacting cilia beat frequency, we show that the increase in cilium length is associated with a decrease in beat amplitude, resulting in similar flow strengths for Arl13b overexpression and wild-type (WT) embryos, which were not predicted by current theory...
March 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28401750/the-ciliary-transition-zone-finding-the-pieces-and-assembling-the-gate
#11
João Gonçalves, Laurence Pelletier
Eukaryotic cilia are organelles that project from the surface of cells to fulfill motility and sensory functions. In vertebrates, the functions of both motile and immotile cilia are critical for embryonic development and adult tissue homeostasis. Importantly, a multitude of human diseases is caused by abnormal cilia biogenesis and functions which rely on the compartmentalization of the cilium and the maintenance of its protein composition. The transition zone (TZ) is a specialized ciliary domain present at the base of the cilium and is part of a gate that controls protein entry and exit from this organelle...
April 12, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28400442/peripherin-diverts-ciliary-ectosome-release-to-photoreceptor-disc-morphogenesis
#12
Robert S Molday, Andrew F X Goldberg
Formation of membrane discs in photoreceptor cells requires evagination of its ciliary plasma membrane by an unknown molecular mechanism. Salinas et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608081) show that peripherin (also known as peripherin-2 or peripherin-2/rds) diverts membrane traffic to photoreceptor disc formation by inhibiting ectosome release from the cilium.
April 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28399904/separation-of-photoreceptor-cell-compartments-in-mouse-retina-for-protein-analysis
#13
Kasey Rose, Steven T Walston, Jeannie Chen
BACKGROUND: Light exposure triggers movement of certain signaling proteins within the cellular compartments of the highly polarized rod photoreceptor cell. This redistribution of proteins between the inner and outer segment compartments affects the performance and physiology of the rod cell. In addition, newly synthesized phototransduction proteins traverse from the site of their synthesis in the inner segment, through the thin connecting cilium, to reach their destination in the outer segment...
April 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28381413/photoreceptor-discs-form-through-peripherin-dependent-suppression-of-ciliary-ectosome-release
#14
Raquel Y Salinas, Jillian N Pearring, Jin-Dong Ding, William J Spencer, Ying Hao, Vadim Y Arshavsky
The primary cilium is a highly conserved organelle housing specialized molecules responsible for receiving and processing extracellular signals. A recently discovered property shared across many cilia is the ability to release small vesicles called ectosomes, which are used for exchanging protein and genetic material among cells. In this study, we report a novel role for ciliary ectosomes in building the elaborate photoreceptor outer segment filled with hundreds of tightly packed "disc" membranes. We demonstrate that the photoreceptor cilium has an innate ability to release massive amounts of ectosomes...
April 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28379564/shortened-primary-cilium-length-and-dysregulated-sonic-hedgehog-signaling-in-niemann-pick-c1-disease
#15
Sonia Canterini, Jessica Dragotto, Andrea Dardis, Stefania Zampieri, Maria Egle De Stefano, Franco Mangia, Robert P Erickson, Maria Teresa Fiorenza
The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder due to mutations in the NPC1 gene, encoding a transmembrane protein related to the Sonic hedgehog receptor, Patched, and involved in intracellular trafficking of cholesterol. We have recently found that the proliferation of cerebellar granule neuron precursors is significantly reduced in Npc1-/- mice due to the downregulation of Shh expression. This finding prompted us to analyze the formation of the primary cilium, a non-motile organelle that is specialized for Shh signal transduction and responsible, when defective, for several human genetic disorders...
April 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28370949/beemer-langer-syndrome-is-a-ciliopathy-due-to-biallelic-mutations-in-ift122
#16
Karina C Silveira, Carolina A Moreno, Denise P Cavalcanti
Since most short-rib polydactyly phenotypes are due to genes involved with biogenesis and maintenance of the primary cilium, this group of skeletal dysplasias was recently designated as ciliopathies with major skeletal involvement. Beemer-Langer syndrome or short-rib polydactyly type IV, was first described in 1983, and has, thus far, remained without a defined molecular basis. The most recent classification of the skeletal dysplasias referred to this phenotype as an as-yet unproven ciliopathy. IFT122 is a gene that encodes a protein responsible for the retrograde transport along the cilium; it has been associated with this group of skeletal dysplasias...
March 28, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28370099/the-electric-fence-to-cell-cycle-progression-do-local-changes-in-membrane-potential-facilitate-disassembly-of-the-primary-cilium-timely-and-localized-expression-of-a-potassium-channel-may-set-the-conditions-that-allow-retraction-of-the-primary-cilium
#17
REVIEW
Diana Urrego, Araceli Sánchez, Adam P Tomczak, Luis A Pardo
Kv10.1 is a voltage-gated potassium channel relevant for tumor biology, but the underlying mechanism is still unclear. We propose that Kv10.1 plays a role coordinating primary cilium disassembly with cell cycle progression through localized changes of membrane potential at the ciliary base. Most non-dividing cells display a primary cilium, an antenna-like structure important for cell physiology. The cilium is disassembled when the cell divides, which requires an increase of Ca(2+) concentration and a redistribution of phospholipids in its basal region, both of which would be facilitated by local hyperpolarization...
March 30, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28360215/correction-for-arl13b-regulates-shh-signaling-from-both-inside-and-outside-the-cilium
#18
(no author information available yet)
No abstract text is available yet for this article.
April 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28346501/a-tissue-specific-role-for-intraflagellar-transport-genes-during-craniofacial-development
#19
Elizabeth N Schock, Jaime N Struve, Ching-Fang Chang, Trevor J Williams, John Snedeker, Aria C Attia, Rolf W Stottmann, Samantha A Brugmann
Primary cilia are nearly ubiquitous, cellular projections that function to transduce molecular signals during development. Loss of functional primary cilia has a particularly profound effect on the developing craniofacial complex, causing several anomalies including craniosynostosis, micrognathia, midfacial dysplasia, cleft lip/palate and oral/dental defects. Development of the craniofacial complex is an intricate process that requires interactions between several different tissues including neural crest cells, neuroectoderm and surface ectoderm...
2017: PloS One
https://www.readbyqxmd.com/read/28342295/intraflagellar-transport-mechanisms-of-motor-action-cooperation-and-cargo-delivery
#20
REVIEW
Bram Prevo, Jonathan M Scholey, Erwin J G Peterman
Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance, and length control of cilia, which play critical roles in motility, sensory reception, and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example, axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium...
March 25, 2017: FEBS Journal
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