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https://www.readbyqxmd.com/read/27816963/defective-ciliogenesis-in-thyroid-h%C3%A3-rthle-cell-tumors-is-associated-with-increased-autophagy
#1
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...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27802276/craniofacial-ciliopathies-reveal-specific-requirements-for-gli-proteins-during-development-of-the-facial-midline
#2
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
#3
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
#4
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
#5
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...
October 13, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27727273/zfp423-regulates-sonic-hedgehog-signaling-via-primary-cilium-function
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27622883/pulsed-electromagnetic-fields-stimulate-osteogenic-differentiation-and-maturation-of-osteoblasts-by-upregulating-the-expression-of-bmprii-localized-at-the-base-of-primary-cilium
#9
Yan-Fang Xie, Wen-Gui Shi, Jian Zhou, Yu-Hai Gao, Shao-Feng Li, Qing-Qing Fang, Ming-Gang Wang, Hui-Ping Ma, Ju-Fang Wang, Cory J Xian, Ke-Ming Chen
Pulsed electromagnetic fields (PEMFs) have been considered as a potential candidate for the prevention and treatment of osteoporosis, however, the mechanism of its action is still elusive. We have previously reported that 50Hz 0.6mT PEMFs stimulate osteoblastic differentiation and mineralization in a primary cilium- dependent manner, but did not know the reason. In the current study, we found that the PEMFs promoted osteogenic differentiation and maturation of rat calvarial osteoblasts (ROBs) by activating bone morphogenetic protein BMP-Smad1/5/8 signaling on the condition that primary cilia were normal...
September 10, 2016: Bone
https://www.readbyqxmd.com/read/27466190/ift52-mutations-destabilize-anterograde-complex-assembly-disrupt-ciliogenesis-and-result-in-short-rib-polydactyly-syndrome
#10
Wenjuan Zhang, S Paige Taylor, Lisette Nevarez, Ralph S Lachman, Deborah A Nickerson, Michael Bamshad, Deborah Krakow, Daniel H Cohn
The short-rib polydactyly syndromes (SRPS) encompass a radiographically and genetically heterogeneous group of skeletal ciliopathies that are characterized by a long narrow chest, short extremities, and variable occurrence of polydactyly. Radiographic abnormalities include undermineralization of the calvarium, shortened and bowed appendicular bones, trident shaped acetabula and polydactyly. In a case of SRPS we identified compound heterozygosity for mutations in IFT52, which encodes a component of the anterograde intraflagellar transport complex...
July 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27435857/silibinin-negatively-contributes-to-primary-cilia-length-via-autophagy-regulated-by-histone-deacetylase-6-in-confluent-mouse-embryo-fibroblast-3t3-l1-cells
#11
Qian Xu, Wei Liu, Xiaoling Liu, Weiwei Liu, Hongju Wang, Guodong Yao, Linghe Zang, Toshihiko Hayashi, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
Primary cilium is a cellular antenna, signalling as a sensory organelle. Numerous pathological manifestation is associated with change of its length. Although the interaction between autophagy and primary cilia has been suggested, the role of autophagy in primary cilia length is largely unknown. In this study the primary cilia were immunostained and observed by using confocal fluorescence microscopy, and we found that silibinin, a natural flavonoid, shortened the length of primary cilia, meanwhile it also induced autophagy in 3T3-L1 cells...
September 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27343245/intraflagellar-transport-is-required-for-the-maintenance-of-the-trypanosome-flagellum-composition-but-not-its-length
#12
Cécile Fort, Serge Bonnefoy, Linda Kohl, Philippe Bastin
Intraflagellar transport (IFT) is required for construction of most cilia and flagella. Here, we used electron microscopy, immunofluorescence and live video microscopy to show that IFT is absent or arrested in the mature flagellum of Trypanosoma brucei upon RNA interference (RNAi)-mediated knockdown of IFT88 and IFT140, respectively. Flagella assembled prior to RNAi did not shorten, showing that IFT is not essential for the maintenance of flagella length. Although the ultrastructure of the axoneme was not visibly affected, flagellar beating was strongly reduced and the distribution of several flagellar components was drastically modified...
August 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27207957/cilia-associated-genes-play-differing-roles-in-aminoglycoside-induced-hair-cell-death-in-zebrafish
#13
Tamara M Stawicki, Liana Hernandez, Robert Esterberg, Tor Linbo, Kelly N Owens, Arish N Shah, Nihal Thapa, Brock Roberts, Cecilia B Moens, Edwin W Rubel, David W Raible
Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio) we have found that mutations in multiple cilia genes implicated in intraflagellar transport (dync2h1, wdr35, ift88, and traf3ip), and the ciliary transition zone (cc2d2a, mks1, and cep290) lead to resistance to aminoglycoside-induced hair cell death...
2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27053191/characterization-of-primary-cilia-during-the-differentiation-of-retinal-ganglion-cells-in-the-zebrafish
#14
Paola Lepanto, Camila Davison, Gabriela Casanova, Jose L Badano, Flavio R Zolessi
BACKGROUND: Retinal ganglion cell (RGC) differentiation in vivo is a highly stereotyped process, likely resulting from the interaction of cell type-specific transcription factors and tissue-derived signaling factors. The primary cilium, as a signaling hub in the cell, may have a role during this process but its presence and localization during RGC generation, and its contribution to the process of cell differentiation, have not been previously assessed in vivo. METHODS: In this work we analyzed the distribution of primary cilia in vivo using laser scanning confocal microscopy, as well as their main ultrastructural features by transmission electron microscopy, in the early stages of retinal histogenesis in the zebrafish, around the time of RGC generation and initial differentiation...
April 6, 2016: Neural Development
https://www.readbyqxmd.com/read/27033521/genome-wide-screen-identifies-novel-machineries-required-for-both-ciliogenesis-and-cell-cycle-arrest-upon-serum-starvation
#15
Ji Hyun Kim, Soo Mi Ki, Je-Gun Joung, Eric Scott, Susanne Heynen-Genel, Pedro Aza-Blanc, Chang Hyuk Kwon, Joon Kim, Joseph G Gleeson, Ji Eun Lee
Biogenesis of the primary cilium, a cellular organelle mediating various signaling pathways, is generally coordinated with cell cycle exit/re-entry. Although the dynamic cell cycle-associated profile of the primary cilium has been largely accepted, the mechanism governing the link between ciliogenesis and cell cycle progression has been poorly understood. Using a human genome-wide RNAi screen, we identify genes encoding subunits of the spliceosome and proteasome as novel regulators of ciliogenesis. We demonstrate that 1) the mRNA processing-related hits are essential for RNA expression of molecules acting in cilia disassembly, such as AURKA and PLK1, and 2) the ubiquitin-proteasome systems (UPS)-involved hits are necessary for proteolysis of molecules acting in cilia assembly, such as IFT88 and CPAP...
June 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26926121/the-bbsome-controls-energy-homeostasis-by-mediating-the-transport-of-the-leptin-receptor-to-the-plasma-membrane
#16
Deng-Fu Guo, Huxing Cui, Qihong Zhang, Donald A Morgan, Daniel R Thedens, Darryl Nishimura, Justin L Grobe, Val C Sheffield, Kamal Rahmouni
Bardet-Biedl syndrome (BBS) is a highly pleiotropic autosomal recessive disorder associated with a wide range of phenotypes including obesity. However, the underlying mechanism remains unclear. Here, we show that neuronal BBSome is a critical determinant of energy balance through its role in the regulation of the trafficking of the long signaling form of the leptin receptor (LRb). Targeted disruption of the BBSome by deleting the Bbs1 gene from the nervous system causes obesity in mice, and this phenotype is reproduced by ablation of the Bbs1 gene selectively in the LRb-expressing cells, but not from adipocytes...
February 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26912722/intraflagellar-transport-proteins-172-80-57-54-38-and-20-form-a-stable-tubulin-binding-ift-b2-complex
#17
Michael Taschner, Kristina Weber, André Mourão, Melanie Vetter, Mayanka Awasthi, Marc Stiegler, Sagar Bhogaraju, Esben Lorentzen
Intraflagellar transport (IFT) relies on the IFT complex and is required for ciliogenesis. The IFT-B complex consists of 9-10 stably associated core subunits and six "peripheral" subunits that were shown to dissociate from the core structure at moderate salt concentration. We purified the six "peripheral"IFT-B subunits of Chlamydomonas reinhardtiias recombinant proteins and show that they form a stable complex independently of the IFT-B core. We suggest a nomenclature of IFT-B1 (core) and IFT-B2 (peripheral) for the two IFT-B subcomplexes...
April 1, 2016: EMBO Journal
https://www.readbyqxmd.com/read/26861287/biological-and-chemical-removal-of-primary-cilia-affects-mechanical-activation-of-chondrogenesis-markers-in-chondroprogenitors-and-hypertrophic-chondrocytes
#18
Matthew E Deren, Xu Yang, Yingjie Guan, Qian Chen
Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26687824/strain-induced-mechanotransduction-through-primary-cilia-extracellular-atp-purinergic-calcium-signaling-and-erk1-2-transactivates-cited2-and-downregulates-mmp-1-and-mmp-13-gene-expression-in-chondrocytes
#19
Z He, D J Leong, Z Zhuo, R J Majeska, L Cardoso, D C Spray, M B Goldring, N J Cobelli, H B Sun
OBJECTIVE: To determine the strain-induced signaling pathways involved in regulating the transactivation of the transcription regulator Cbp/p300 Interacting Transactivator with ED-rich tail 2 (CITED2) and downstream targets in chondrocytes. METHODS: Primary human chondrocytes or C28/I2 chondrocytic cells were subjected to various strain regimes. C57BL/6 mice were subjected to treadmill running. Loss-of-function was carried out using siRNA or inhibitors specific for targeted molecules...
May 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/26542012/primary-cilia-are-critical-for-sonic-hedgehog-mediated-dopaminergic-neurogenesis-in-the-embryonic-midbrain
#20
Mary Gazea, Evangelia Tasouri, Marianna Tolve, Viktoria Bosch, Anna Kabanova, Christian Gojak, Bahtiyar Kurtulmus, Orna Novikov, Joachim Spatz, Gislene Pereira, Wolfgang Hübner, Claude Brodski, Kerry L Tucker, Sandra Blaess
Midbrain dopaminergic (mDA) neurons modulate various motor and cognitive functions, and their dysfunction or degeneration has been implicated in several psychiatric diseases. Both Sonic Hedgehog (Shh) and Wnt signaling pathways have been shown to be essential for normal development of mDA neurons. Primary cilia are critical for the development of a number of structures in the brain by serving as a hub for essential developmental signaling cascades, but their role in the generation of mDA neurons has not been examined...
January 1, 2016: Developmental Biology
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