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https://www.readbyqxmd.com/read/29743590/loss-of-function-of-ift88-determines-metabolic-phenotypes-in-thyroid-cancer
#1
Junguee Lee, Shinae Yi, Minho Won, Young Shin Song, Hyon-Seung Yi, Young Joo Park, Ki Cheol Park, Jung Tae Kim, Joon Young Chang, Min Joung Lee, Hae Joung Sul, Ji Eun Choi, Koon Soon Kim, Jukka Kero, Joon Kim, Minho Shong
Primary cilia are microtubule-based, dynamic organelles characterized by continuous assembly and disassembly. The intraflagellar transport (IFT) machinery, including IFT88 in cilia, is involved in the maintenance of bidirectional motility along the axonemes, which is required for ciliogenesis and functional competence. Cancer cells are frequently associated with loss of primary cilia and IFT functions. However, there is little information on the role of IFT88 or primary cilia in the metabolic remodeling of cancer cells...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29702220/dicam-promotes-proliferation-and-maturation-of-chondrocyte-through-indian-hedgehog-signaling-in-primary-cilia
#2
S Han, H-R Park, E-J Lee, J-A Jang, M-S Han, G-W Kim, J-H Jeong, J-Y Choi, F Beier, Y-K Jung
OBJECTIVES: Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a novel function as a modulator of primary cilia-mediated Indian hedgehog (Ihh) signaling in chondrocytes. METHODS: Cartilage-specific Dicam transgenic mouse was constructed and the phenotype of growth plates at embryonic day 15...
April 25, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29658664/-primary-cilium-acts-as-an-oxygen-sensor-in-pc12-cells
#3
Yuhai Gao, Xinzhu Qi, Jian Zhou, Xin Wang, Keming Chen, Huiping Ma
<b>Objective:</b> To investigate the function of primary cilium as an oxygen sensor in PC12 cells. <b>Methods:</b> The PC12 cells were transfected with IFT88 siRNA. The nuclear translocation of hypoxia inducible factor-1α (HIF-1α), nuclear factor erythroid-2 related factor 2 (Nrf2), and ciliogenesis were observed by immunofluorescence staining; and the mRNA expressions of <i>HIF-1α, Nrf2</i>, vascular endothelial growth factor (<i>VEGF</i>) and superoxide dismutase (<i>SOD</i>) were detected by real-time RT-PCR...
May 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/29568513/assaying-sensory-ciliopathies-using-calcium-biosensor-expression-in-zebrafish-ciliated-olfactory-neurons
#4
Judith G M Bergboer, Cameron Wyatt, Christina Austin-Tse, Emre Yaksi, Iain A Drummond
Background: Primary cilia mediate signal transduction by acting as an organizing scaffold for receptors, signalling proteins and ion channels. Ciliated olfactory sensory neurons (OSNs) organize olfactory receptors and ion channels on cilia and generate a calcium influx as a primary signal in odourant detection. In the zebrafish olfactory placode, ciliated OSNs and microvillus OSNs constitute the major OSN cell types with distinct odourant sensitivity. Methods: Using transgenic expression of the calcium biosensor GCaMP5 in OSNs, we analysed sensory cilia-dependent odour responses in live zebrafish, at individual cell resolution...
2018: Cilia
https://www.readbyqxmd.com/read/29500191/primary-cilia-sensitize-endothelial-cells-to-bmp-and-prevent-excessive-vascular-regression
#5
Anne-Clémence Vion, Silvanus Alt, Alexandra Klaus-Bergmann, Anna Szymborska, Tuyu Zheng, Tijana Perovic, Adel Hammoutene, Marta Bastos Oliveira, Eireen Bartels-Klein, Irene Hollfinger, Pierre-Emmanuel Rautou, Miguel O Bernabeu, Holger Gerhardt
Blood flow shapes vascular networks by orchestrating endothelial cell behavior and function. How endothelial cells read and interpret flow-derived signals is poorly understood. Here, we show that endothelial cells in the developing mouse retina form and use luminal primary cilia to stabilize vessel connections selectively in parts of the remodeling vascular plexus experiencing low and intermediate shear stress. Inducible genetic deletion of the essential cilia component intraflagellar transport protein 88 (IFT88) in endothelial cells caused premature and random vessel regression without affecting proliferation, cell cycle progression, or apoptosis...
May 7, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29477141/increased-primary-cilia-in-idiopathic-pulmonary-fibrosis
#6
Junguee Lee, Dong Hyun Oh, Ki Cheol Park, Ji Eun Choi, Jong Beom Kwon, Jongho Lee, Kuhn Park, Hae Joung Sul
Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue...
March 31, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29396292/dynarrestin-a-novel-inhibitor-of-cytoplasmic-dynein
#7
Susanne Höing, Ting-Yu Yeh, Matthias Baumann, Nancy E Martinez, Peter Habenberger, Lea Kremer, Hannes C A Drexler, Philipp Küchler, Peter Reinhardt, Axel Choidas, Mia-Lisa Zischinsky, Gunther Zischinsky, Swaran Nandini, Aaron P Ledray, Stephanie A Ketcham, Lydia Reinhardt, Masin Abo-Rady, Michael Glatza, Stephen J King, Peter Nussbaumer, Slava Ziegler, Bert Klebl, Trina A Schroer, Hans R Schöler, Herbert Waldmann, Jared Sterneckert
Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh signaling downstream of Smo are urgently needed. We identified dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly to inhibit cytoplasmic dynein 1-dependent microtubule binding and motility in vitro without affecting ATP hydrolysis. It rapidly and reversibly inhibits endosome movement in living cells and perturbs mitosis by inducing spindle misorientation and pseudoprometaphase delay...
April 19, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29393439/role-of-ift88-in-icariin%C3%A2-regulated-maintenance-of-the-chondrocyte-phenotype
#8
Wei Xiang, Jiaming Zhang, Rui Wang, Limei Wang, Shengjie Wang, Yingxing Wu, Yonghui Dong, Fengjing Guo, Tao Xu
Maintenance of the chondrocyte phenotype is crucial for cartilage repair during tissue engineering. Intraflagellar transport protein 88 (IFT88) is an essential component of primary cilia, shuttling signals along the axoneme. The hypothesis of the present study was that IFT88 could exert an important role in icariin‑regulated maintenance of the chondrocyte phenotype. To this end, the effects of icariin on proliferation and differentiation of the chondrogenic cell line, ATDC5, were explored. Icariin‑treated ATDC5 cells and primary chondrocytes expressed IFT88...
April 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29236364/intraflagellar-transporter-protein-140-ift140-a-component-of-ift-a-complex-is-essential-for-male-fertility-and-spermiogenesis-in-mice
#9
Yong Zhang, Hong Liu, Wei Li, Zhengang Zhang, Shiyang Zhang, Maria E Teves, Courtney Stevens, James A Foster, Gregory E Campbell, Jolene J Windle, Rex A Hess, Gregory J Pazour, Zhibing Zhang
Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. However, little is known about its role in sperm flagella formation and male fertility. IFT140 is a component of IFT-A complex. In mouse, it is highly expressed in the testis. Ift140 gene was inactivated specifically in mouse spermatocytes/spermatids. The mutant mice did not show any gross abnormalities, but all were infertile and associated with significantly reduced sperm number and motility...
February 2018: Cytoskeleton
https://www.readbyqxmd.com/read/29228333/dnaaf1-links-heart-laterality-with-the-aaa-atpase-ruvbl1-and-ciliary-intraflagellar-transport
#10
Verity L Hartill, Glenn van de Hoek, Mitali P Patel, Rosie Little, Christopher M Watson, Ian R Berry, Amelia Shoemark, Dina Abdelmottaleb, Emma Parkes, Chiara Bacchelli, Katarzyna Szymanska, Nine V Knoers, Peter J Scambler, Marius Ueffing, Karsten Boldt, Robert Yates, Paul J Winyard, Beryl Adler, Eduardo Moya, Louise Hattingh, Anil Shenoy, Claire Hogg, Eamonn Sheridan, Ronald Roepman, Dominic Norris, Hannah M Mitchison, Rachel H Giles, Colin A Johnson
DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p...
February 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29203870/ift-proteins-spatially-control-the-geometry-of-cleavage-furrow-ingression-and-lumen-positioning
#11
Nicolas Taulet, Benjamin Vitre, Christelle Anguille, Audrey Douanier, Murielle Rocancourt, Michael Taschner, Esben Lorentzen, Arnaud Echard, Benedicte Delaval
Cytokinesis mediates the physical separation of dividing cells and, in 3D epithelia, provides a spatial landmark for lumen formation. Here, we unravel an unexpected role in cytokinesis for proteins of the intraflagellar transport (IFT) machinery, initially characterized for their ciliary role and their link to polycystic kidney disease. Using 2D and 3D cultures of renal cells, we show that IFT proteins are required to correctly shape the central spindle, to control symmetric cleavage furrow ingression and to ensure central lumen positioning...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29089388/the-flavonol-glycoside-icariin-promotes-bone-formation-in-growing-rats-by-activating-the-camp-signaling-pathway-in-primary-cilia-of-osteoblasts
#12
Wengui Shi, Yuhai Gao, Yuanyuan Wang, Jian Zhou, Zhenlong Wei, Xiaoni Ma, Huiping Ma, Cory J Xian, Jufang Wang, Keming Chen
Icariin, a prenylated flavonol glycoside isolated from the herb Epimedium , has been considered as a potential alternative therapy for osteoporosis. Previous research has shown that, unlike other flavonoids, icariin is unlikely to act via the estrogen receptor, but its exact mechanism of action is unknown. In this study, using rat calvarial osteoblast culture and rat bone growth models, we demonstrated that icariin promotes bone formation by activating the cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway requiring functional primary cilia of osteoblasts...
December 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29089384/the-guanine-nucleotide-exchange-factor-arf-like-protein-13b-is-essential-for-assembly-of-the-mouse-photoreceptor-transition-zone-and-outer-segment
#13
Christin Hanke-Gogokhia, Zhijian Wu, Ali Sharif, Hussein Yazigi, Jeanne M Frederick, Wolfgang Baehr
Arf-like protein 13b (ARL13b) is a small GTPase that functions as a guanosine nucleotide exchange factor (GEF) for ARL3-GDP. ARL13b is located exclusively in photoreceptor outer segments (OS) presumably anchored to discs by palmitoylation, whereas ARL3 is an inner segment cytoplasmic protein. Hypomorphic mutations affecting the ARL13b G-domain inactivate GEF activity and lead to Joubert syndrome (JS) in humans. However, the molecular mechanisms in ARL13b mutation-induced Joubert syndrome, particularly the function of primary cilia, are still incompletely understood...
December 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29066540/tgf-%C3%AE-receptor-i-ii-trafficking-and-signaling-at-primary-cilia-are-inhibited-by-ceramide-to-attenuate-cell-migration-and-tumor-metastasis
#14
Salih Gencer, Natalia Oleinik, Jisun Kim, Shanmugam Panneer Selvam, Ryan De Palma, Mohammed Dany, Rose Nganga, Raquela J Thomas, Can E Senkal, Philip H Howe, Besim Ogretmen
Signaling by the transforming growth factor-β (TGF-β) receptors I and II (TβRI/II) and the primary cilia-localized sonic hedgehog (Shh) pathway promote cell migration and, consequently, tumor metastasis. In contrast, the sphingolipid ceramide inhibits cell proliferation and tumor metastasis. We investigated whether ceramide metabolism inhibited TβRI/II trafficking to primary cilia to attenuate cross-talk between TβRI/II and the Shh pathway. We found that ceramide synthase 4 (CerS4)-generated ceramide stabilized the association between TβRI and the inhibitory factor Smad7, which limited the trafficking of TβRI/II to primary cilia...
October 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/29061117/diatom-flagellar-genes-and-their-expression-during-sexual-reproduction-in-leptocylindrus-danicus
#15
Deepak Nanjappa, Remo Sanges, Maria I Ferrante, Adriana Zingone
BACKGROUND: Flagella have been lost in the vegetative phase of the diatom life cycle, but they are still present in male gametes of centric species, thereby representing a hallmark of sexual reproduction. This process, besides maintaining and creating new genetic diversity, in diatoms is also fundamental to restore the maximum cell size following its reduction during vegetative division. Nevertheless, sexual reproduction has been demonstrated in a limited number of diatom species, while our understanding of its different phases and of their genetic control is scarce...
October 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28981158/low-intensity-pulsed-ultrasound-stimulation-promotes-osteoblast-differentiation-through-hedgehog-signaling
#16
Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Pang Pai, Yuu Horikiri, Nobuyuki Yamanaka, Masaharu Takigawa, Akira Sasaki
Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group...
June 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28954202/ciliopathy-protein-tmem107-plays-multiple-roles-in-craniofacial-development
#17
P Cela, M Hampl, N A Shylo, K J Christopher, M Kavkova, M Landova, T Zikmund, S D Weatherbee, J Kaiser, M Buchtova
A broad spectrum of human diseases called ciliopathies is caused by defective primary cilia morphology or signal transduction. The primary cilium is a solitary organelle that responds to mechanical and chemical stimuli from extracellular and intracellular environments. Transmembrane protein 107 (TMEM107) is localized in the primary cilium and is enriched at the transition zone where it acts to regulate protein content of the cilium. Mutations in TMEM107 were previously connected with oral-facial-digital syndrome, Meckel-Gruber syndrome, and Joubert syndrome exhibiting a range of ciliopathic defects...
January 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#18
REVIEW
Emily R Moore, Christopher R Jacobs
The primary cilium is a solitary, antenna-like sensory organelle with many important roles in cartilage and bone development, maintenance, and function. The primary cilium's potential role as a signaling nexus in the growth plate makes it an attractive therapeutic target for diseases and disorders associated with bone development and maintenance. Many signaling pathways that are mediated by the cilium-such as Hh, Wnt, Ihh/PTHrP, TGFβ, BMP, FGF, and Notch-are also known to influence endochondral ossification, primarily by directing growth plate formation and chondrocyte behavior...
February 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28901443/basic-fibroblast-growth-factor-increases-ift88-expression-in-chondrocytes
#19
Daolu Zhan, Wei Xiang, Fengjing Guo, Yuanzheng Ma
Intraflagellar transport protein 88 (IFT88) is protein crucial for the assembly and maintenance of primary cilia in chondrocytes. Primary cilia regulate mechanical and chemical signals in chondrocytes; however, the effects of cytokines on IFT88 expression and cilia formation and maintenance remain to be elucidated. Therefore, the role of basic fibroblast growth factor (bFGF) on IFT88 expression were examined in theATDC5 murine chondrocytic line, in order to investigate the signaling pathways involved in this process...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900213/copine-7-binds-to-the-cell-surface-receptor-nucleolin-and-regulates-ciliogenesis-and-dspp-expression-during-odontoblast-differentiation
#20
You-Mi Seo, Su-Jin Park, Hye-Kyung Lee, Joo-Cheol Park
Tooth development is a progressive process regulated by interactions between epithelial and mesenchymal tissues. Our previous studies showed that copine-7 (Cpne7), a dental epithelium-derived protein, is a signalling molecule that is secreted by preameloblasts and regulates the differentiation of preodontoblasts into odontoblasts. However, the mechanisms involved in the translocation of Cpne7 from preameloblasts to preodontoblasts and the functions of Cpne7 during odontogenesis are poorly understood. Here, we showed that the internalization of Cpne7 was mediated primarily by caveolae...
September 12, 2017: Scientific Reports
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