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https://www.readbyqxmd.com/read/28500304/microgravity-induces-inhibition-of-osteoblastic-differentiation-and-mineralization-through-abrogating-primary-cilia
#1
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/28489570/transcriptome-profiling-identify-a-recurrent-cryl1-ift88-chimeric-transcript-in-hepatocellular-carcinoma
#2
Yi Huang, Jiaying Zheng, Dunyan Chen, Feng Li, Wenbing Wu, Xiaoli Huang, Yanan Wu, Yangyang Deng, Funan Qiu
We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC patients were recruited and differentially expressed genes (DEGs) were identified. Candidate fusion transcripts were also identified. A total of 1943 DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and enriched in ten pathways including cell cycle, DNA replication, p53, complement and coagulation cascades, etc. Seven candidate fusion genes were detected and CRYL1-IFT88 was successfully validated in the discovery sequencing sample and another 5 tumor samples with the recurrent rate of about 9...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468945/primary-cilia-control-the-maturation-of-tubular-lumen-in-renal-collecting-duct-epithelium
#3
Thomas Ernandez, Olga Komarynets, Alexandra Chassot, Soushma Sougoumarin, Priscilla Soulie, Yubao Wang, Roberto Montesano, Eric Feraille
The key role of the primary cilium in developmental processes is illustrated by ciliopathies resulting from genetic defects of its components. Ciliopathies include a large variety of dysmorphic syndromes that share in common the presence of multiple kidney cysts. These observations suggest that primary cilia may control morphogenetic processes in the developing kidney. In this study, we assessed the role of primary cilium in branching tubulogenesis and/or lumen development using kidney collecting duct-derived mCCDN21 cells that display spontaneous tubulogenic properties when grown in collagen/matrigel matrix...
May 3, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28352462/fixation-methods-can-differentially-affect-ciliary-protein-immunolabeling
#4
Kiet Hua, Russell J Ferland
BACKGROUND: Primary cilia are immotile, microtubule-based organelles present on most cells. Defects in primary cilia presence/function result in a category of developmental diseases referred to as ciliopathies. As the cilia field progresses, there is a need to consider both the ciliary and extraciliary roles of cilia proteins. However, traditional fixation methods are not always suitable for examining the full range of localizations of cilia proteins. Here, we tested a variety of fixation methods with commonly used cilia markers to determine the most appropriate fixation method for different cilia proteins...
2017: Cilia
https://www.readbyqxmd.com/read/28346501/a-tissue-specific-role-for-intraflagellar-transport-genes-during-craniofacial-development
#5
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/28302912/intraflagellar-transport-protein-ift52-recruits-ift46-to-the-basal-body-and-flagella
#6
Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, Kaiyao Huang
Cilia are microtubule based organelles and perform motile, sensing and signaling functions. The assembly and maintenance of cilia depend on intraflagellar transport. Besides ciliary localization, most IFT proteins accumulate at basal bodies. However, little is known about the molecular mechanism of basal body targeting of IFT proteins. We first identified the possible basal body targeting sequence of IFT46 by expressing IFT46 truncations in ift46-1 mutant. The C-terminal sequence 246-321 aa, termed BBTS3, was sufficient to target YFPs to basal bodies in ift46-1 Interestingly, BBTS3 is also responsible for the ciliary targeting of IFT46...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28291836/unique-spatiotemporal-requirements-for-intraflagellar-transport-genes-during-forebrain-development
#7
John Snedeker, Elizabeth N Schock, Jamie N Struve, Ching-Fang Chang, Megan Cionni, Pamela V Tran, Samantha A Brugmann, Rolf W Stottmann
Primary cilia are organelles extended from virtually all cells and are required for the proper regulation of a number of canonical developmental pathways. The role in cortical development of proteins important for ciliary form and function is a relatively understudied area. Here we have taken a genetic approach to define the role in forebrain development of three intraflagellar transport proteins known to be important for primary cilia function. We have genetically ablated Kif3a, Ift88, and Ttc21b in a series of specific spatiotemporal domains...
2017: PloS One
https://www.readbyqxmd.com/read/28264835/ift56-regulates-vertebrate-developmental-patterning-by-maintaining-iftb-complex-integrity-and-ciliary-microtubule-architecture
#8
Daisy Xin, Kasey J Christopher, Lewie Zeng, Yong Kong, Scott D Weatherbee
Cilia are key regulators of animal development and depend on intraflagellar transport (IFT) proteins for their formation and function, yet the roles of individual IFT proteins remain unclear. We examined the Ift56(hop) mouse mutant and reveal novel insight into the function of IFT56, a poorly understood IFTB protein. Ift56(hop) mice have normal cilia distribution but display defective cilia structure, including abnormal positioning and number of ciliary microtubule doublets. We show that Ift56(hop) cilia are unable to accumulate Gli proteins efficiently, resulting in developmental patterning defects in Shh signaling-dependent tissues such as the limb and neural tube...
April 15, 2017: Development
https://www.readbyqxmd.com/read/28179459/practical-method-for-targeted-disruption-of-cilia-related-genes-by-using-crispr-cas9-mediated-homology-independent-knock-in-system
#9
Yohei Katoh, Saki Michisaka, Shohei Nozaki, Teruki Funabashi, Tomoaki Hirano, Ryota Takei, Kazuhisa Nakayama
The CRISPR/Cas9 system has revolutionized genome editing in virtually all organisms. Although the CRISPR/Cas9 system enables the targeted cleavage of genomic DNA, its use for gene knock-in remains challenging because levels of homologous recombination activity vary among various cells. In contrast, the efficiency of homology-independent DNA repair is relatively high in most cell types. Therefore the use of a homology-independent repair mechanism is a possible alternative for efficient genome editing. Here we constructed a donor knock-in vector optimized for the CRISPR/Cas9 system and developed a practical system that enables efficient disruption of target genes by exploiting homology-independent repair...
April 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28154159/the-t-cell-ift20-interactome-reveals-new-players-in-immune-synapse-assembly
#10
Donatella Galgano, Anna Onnis, Elisa Pappalardo, Federico Galvagni, Oreste Acuto, Cosima T Baldari
Sustained signalling at the immune synapse (IS) requires the synaptic delivery of recycling endosome-associated T cell antigen receptors (TCRs). IFT20, a component of the intraflagellar transport system, controls TCR recycling to the IS as a complex with IFT57 and IFT88. Here, we used quantitative mass spectrometry to identify additional interaction partners of IFT20 in Jurkat T cells. In addition to IFT57 and IFT88, the analysis revealed new binding partners, including IFT54 (also known as TRAF3IP1), GMAP-210 (also known as TRIP11), Arp2/3 complex subunit-3 (ARPC3), COP9 signalosome subunit-1 (CSN1, also known as GPS1) and ERGIC-53 (also known as LMAN1)...
March 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28115485/ick-ciliary-kinase-is-essential-for-planar-cell-polarity-formation-in-inner-ear-hair-cells-and-hearing-function
#11
Shio Okamoto, Taro Chaya, Yoshihiro Omori, Ryusuke Kuwahara, Shun Kubo, Hirofumi Sakaguchi, Takahisa Furukawa
Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells, which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each hair cell, exhibit a typical form of PCP. While connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069795/intraflagellar-transport-88-ift88-is-crucial-for-craniofacial-development-in-mice-and-is-a-candidate-gene-for-human-cleft-lip-and-palate
#12
Hua Tian, Jifan Feng, Jingyuan Li, Thach-Vu Ho, Yuan Yuan, Yang Liu, Frederick Brindopke, Jane C Figueiredo, William Magee, Pedro A Sanchez-Lara, Yang Chai
Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G > C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27816963/defective-ciliogenesis-in-thyroid-h%C3%A3-rthle-cell-tumors-is-associated-with-increased-autophagy
#13
Junguee Lee, Shinae Yi, Yea Eun Kang, Joon Young Chang, Jung Tae Kim, Hae Joung Sul, Jong Ok Kim, Jin Man Kim, Joon Kim, Anna Maria Porcelli, Koon Soon Kim, Minho Shong
Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27802276/craniofacial-ciliopathies-reveal-specific-requirements-for-gli-proteins-during-development-of-the-facial-midline
#14
Ching-Fang Chang, Ya-Ting Chang, Grethel Millington, Samantha A Brugmann
Ciliopathies represent a broad class of disorders that affect multiple organ systems. The craniofacial complex is among those most severely affected when primary cilia are not functional. We previously reported that loss of primary cilia on cranial neural crest cells, via a conditional knockout of the intraflagellar transport protein KIF3a, resulted in midfacial widening due to a gain of Hedgehog (HH) activity. Here, we examine the molecular mechanism of how a loss of primary cilia can produce facial phenotypes associated with a gain of HH function...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27770387/primary-cilium-is-required-for-the-stimulating-effect-of-icaritin-on-osteogenic-differentiation-and-mineralization-of-osteoblasts-in-vitro
#15
X-N Ma, C-X Ma, W-G Shi, J Zhou, H-P Ma, Y-H Gao, C J Xian, K-M Chen
OBJECTIVE: Icaritin, one effective metabolite of Herba Epimedii-derived flavonoid icariin, has a strong osteogenic activity. However, its action mechanism remains unclear. Since primary cilia have been shown to play a pivotal role in regulating the osteogenesis, we hypothesized primary cilia are indispensable in mediating icaritin osteogenic effect. MATERIALS AND METHODS: Primary rat calvarial osteoblasts were transfected with siRNA1 targeting intraflagellar transport protein 88 (IFT88), a protein required for ciliogenesis, to prevent formation of primary cilium and were treated with 10(-6) M icaritin...
October 21, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27767179/the-serologically-defined-colon-cancer-antigen-3-sdccag3-is-involved-in-the-regulation-of-ciliogenesis
#16
Fangyan Yu, Shruti Sharma, Agnieszka Skowronek, Kai Sven Erdmann
A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27736039/primary-cilium-regulated-eg-vegf-signaling-facilitates-trophoblast-invasion
#17
Chia-Yih Wang, Hui-Ling Tsai, Jhih-Siang Syu, Ting-Yu Chen, Mei-Tsz Su
Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia...
June 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27727273/zfp423-regulates-sonic-hedgehog-signaling-via-primary-cilium-function
#18
Chen-Jei Hong, Bruce A Hamilton
Zfp423 encodes a 30-zinc finger transcription factor that intersects several canonical signaling pathways. Zfp423 mutations result in ciliopathy-related phenotypes, including agenesis of the cerebellar vermis in mice and Joubert syndrome (JBTS19) and nephronophthisis (NPHP14) in humans. Unlike most ciliopathy genes, Zfp423 encodes a nuclear protein and its developmental expression is complex, leading to alternative proposals for cellular mechanisms. Here we show that Zfp423 is expressed by cerebellar granule cell precursors, that loss of Zfp423 in these precursors leads to cell-intrinsic reduction in proliferation, loss of response to Shh, and primary cilia abnormalities that include diminished frequency of both Smoothened and IFT88 localization...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27682589/intraflagellar-transport-protein-ift20-is-essential-for-male-fertility-and-spermiogenesis-in-mice
#19
Zhengang Zhang, Wei Li, Yong Zhang, Ling Zhang, Maria E Teves, Hong Liu, Jerome F Strauss, Gregory J Pazour, James A Foster, Rex A Hess, Zhibing Zhang
Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules...
September 28, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27681595/loss-of-ift122-a-retrograde-intraflagellar-transport-ift-complex-component-leads-to-slow-progressive-photoreceptor-degeneration-due-to-inefficient-opsin-transport
#20
Meriam Boubakri, Taro Chaya, Hiromi Hirata, Naoko Kajimura, Ryusuke Kuwahara, Akiko Ueno, Jarema Malicki, Takahisa Furukawa, Yoshihiro Omori
In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system that mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A...
November 18, 2016: Journal of Biological Chemistry
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