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https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#1
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...
September 13, 2017: 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
#2
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...
September 8, 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
#3
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
https://www.readbyqxmd.com/read/28706295/dgk%C3%AE-triggers-endoplasmic-reticulum-release-of-ift88-containing-vesicles-destined-for-the-assembly-of-primary-cilia
#4
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
https://www.readbyqxmd.com/read/28671279/impairment-of-primary-cilia-contributes-to-visceral-adiposity-of-high-fat-diet-fed-mice
#5
Ni Qiu, Wei-Jin Fang, Hong-Sheng Li, Zhi-Min He, Zhou-Sheng Xiao, Yan Xiong
Deficiency of primary cilia formation by knockout kinesin family member 3A (Kif3a) in mature osteoblasts led to osteopenia and enhanced adipogenesis. Adipogenesis plays an important role in adipose tissue expansion by High-fat-diet (HFD) induced obesity. Whether primary cilia participate in high-fat-diet induced adiposity remains unclear. In this study, we found that the number and length of primary cilia and expression levels of KIF3A and intraflagellar transport 88 homolog (IFT88) mRNA and proteins reached peak on the day 3 of adipogenesis, followed by a decrease to reach low basal expression levels at day 9 when differentiated to lipid accumulating adipocytes in VAT-SVFs derived from lean mice...
July 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28607127/role-of-the-primary-cilia-on-the-macula-densa-and-thick-ascending-limbs-in-regulation-of-sodium-excretion-and-hemodynamics
#6
Jiangping Song, Lei Wang, Fan Fan, Jin Wei, Jie Zhang, Yan Lu, Yiling Fu, Shaohui Wang, Luis A Juncos, Ruisheng Liu
We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2(CRE); IFT88Δ(/flox)), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus...
August 2017: Hypertension
https://www.readbyqxmd.com/read/28586053/hdac6-inhibition-suppresses-chondrosarcoma-by-restoring-the-expression-of-primary-cilia
#7
Wei Xiang, Fengjing Guo, Weiting Cheng, Jiaming Zhang, Junming Huang, Rui Wang, Zhongxi Ma, Kai Xu
Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6...
June 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28556366/a-role-for-primary-cilia-in-aortic-valve-development-and-disease
#8
Katelynn A Toomer, Diana Fulmer, Lilong Guo, Alex Drohan, Neal Peterson, Paige Swanson, Brittany Brooks, Rupak Mukherjee, Simon Body, Joshua H Lipschutz, Andy Wessels, Russell A Norris
BACKGROUND: Bicuspid aortic valve (BAV) disease is the most common congenital heart defect, affecting 0.5-1.2% of the population and causing significant morbidity and mortality. Only a few genes have been identified in pedigrees, and no single gene model explains BAV inheritance, thus supporting a complex genetic network of interacting genes. However, patients with rare syndromic diseases that stem from alterations in the structure and function of primary cilia ("ciliopathies") exhibit BAV as a frequent cardiovascular finding, suggesting primary cilia may factor broadly in disease etiology...
August 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28500304/microgravity-induces-inhibition-of-osteoblastic-differentiation-and-mineralization-through-abrogating-primary-cilia
#9
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-identifies-a-recurrent-cryl1-ift88-chimeric-transcript-in-hepatocellular-carcinoma
#10
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...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468945/primary-cilia-control-the-maturation-of-tubular-lumen-in-renal-collecting-duct-epithelium
#11
Thomas Ernandez, Olga Komarynets, Alexandra Chassot, Soushma Sougoumarin, Priscilla Soulié, 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...
July 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28352462/fixation-methods-can-differentially-affect-ciliary-protein-immunolabeling
#12
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
#13
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
#14
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 (IFT). 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 in IFT46 by expressing IFT46 truncation constructs in an ift46-1 mutant. The C-terminal sequence between residues 246-321, termed BBTS3, was sufficient to target YFP to basal bodies in the ift46-1 strain...
May 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28291836/unique-spatiotemporal-requirements-for-intraflagellar-transport-genes-during-forebrain-development
#15
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
#16
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
#17
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
#18
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
#19
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 (HCs), 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 HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood...
February 22, 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
#20
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
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