keyword
https://read.qxmd.com/read/38464172/the-primary-cilium-and-its-hedgehog-signaling-in-nociceptors-contribute-to-inflammatory-and-neuropathic-pain
#1
Kerry Tucker, Lindsey Fitzsimons, Larissa Staurengo-Ferrari, Oliver Bogen, Dioneia Araldi, Ivan Bonet, Ethan Jordan, Jon Levine
The primary cilium, a 1-3 μm long hair-like structure protruding from the surface of almost all cells in the vertebrate body, is critical for neuronal development and also functions in the adult. As the migratory neural crest settles into dorsal root ganglia (DRG) sensory neurons elaborate a single primary cilium at their soma that is maintained into adult stages. While it is not known if primary cilia are expressed in nociceptors, or their potential function in the mature DRG neuron, recent studies have shown a role for Hedgehog, whose signaling demonstrates a dependence on primary cilia, in nociceptor sensitization...
February 26, 2024: Research Square
https://read.qxmd.com/read/38413974/primary-cilia-promote-the-differentiation-of-human-neurons-through-the-wnt-signaling-pathway
#2
JOURNAL ARTICLE
Andrea Coschiera, Masahito Yoshihara, Gilbert Lauter, Sini Ezer, Mariangela Pucci, Haonan Li, Alan Kavšek, Christian G Riedel, Juha Kere, Peter Swoboda
BACKGROUND: Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell's immediate environment: signal reception and transduction to/from the ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies and certain neurodevelopmental disorders. In the developing brain cilia play well-documented roles for the expansion of the neural progenitor cell pool, while information about the roles of cilia during post-mitotic neuron differentiation and maturation is scarce...
February 27, 2024: BMC Biology
https://read.qxmd.com/read/38373798/ift88-maintains-sensory-function-by-localising-signalling-proteins-along-drosophila-cilia
#3
JOURNAL ARTICLE
Sascha Werner, Pilar Okenve-Ramos, Philip Hehlert, Sihem Zitouni, Pranjali Priya, Susana Mendonça, Anje Sporbert, Christian Spalthoff, Martin C Göpfert, Swadhin Chandra Jana, Mónica Bettencourt-Dias
Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show Drosophila melanogaste r IFT88 ( Dm IFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in Drosophila hearing and negative-gravitaxis behaviour, and a yet uncharacterised Drosophila Guanylyl Cyclase 2d ( Dm Gucy2d/CG34357) as Dm IFT88 cargoes...
May 2024: Life Science Alliance
https://read.qxmd.com/read/38359483/naringenin-attenuated-airway-cilia-structural-and-functional-injury-induced-by-cigarette-smoke-extract-via-il-17-and-camp-pathways
#4
JOURNAL ARTICLE
Jiashuo Zhang, Weiyang Fan, Hao Wu, Yue Yao, Linlin Jin, Ruiqi Chen, Ziyan Xu, Weiwei Su, Yonggang Wang, Peibo Li
BACKGROUND: Cigarette smoke impairs mucociliary clearance via mechanisms such as inflammatory response and oxidative injury, which in turn induces various respiratory diseases. Naringenin, a naturally occurring flavonoid in grapes and grapefruit, has exhibited pharmacological properties such as anti-inflammatory, expectorant, and antioxidant properties. However, it is still unclear whether naringenin protects airway cilia from injury caused by cigarette smoke. PURPOSE: This study aimed to investigate the effect of naringenin on cigarette smoke extract (CSE)-induced structural and functional abnormalities in airway cilia and highlight the potential regulatory mechanism...
September 2, 2023: Phytomedicine
https://read.qxmd.com/read/38357357/signatures-of-selection-in-mulinia-lateralis-underpinning-its-rapid-adaptation-to-laboratory-conditions
#5
JOURNAL ARTICLE
Zujing Yang, Ang Zhao, Mingxuan Teng, Moli Li, Hao Wang, Xuefeng Wang, Zhi Liu, Qifan Zeng, Liping Hu, Jingjie Hu, Zhenmin Bao, Xiaoting Huang
The dwarf surf clam, Mulinia lateralis , is considered as a model species for bivalves because of its rapid growth and short generation time. Recently, successful breeding of this species for multiple generations in our laboratory revealed its acquisition of adaptive advantages during artificial breeding. In this study, 310 individuals from five different generations were genotyped with 22,196 single nucleotide polymorphisms (SNPs) with the aim of uncovering the genetic basis of their adaptation to laboratory conditions...
February 2024: Evolutionary Applications
https://read.qxmd.com/read/38351372/xiap-mediated-degradation-of-ift88-disrupts-hsc-cilia-to-stimulate-hsc-activation-and-liver-fibrosis
#6
JOURNAL ARTICLE
Renjie Hong, Yanjie Tan, Xiaoyu Tian, Zhenzhou Huang, Jiaying Wang, Hua Ni, Jia Yang, Weiwen Bu, Song Yang, Te Li, Fan Yu, Weilong Zhong, Tao Sun, Xiaohong Wang, Dengwen Li, Min Liu, Yunfan Yang, Jun Zhou
Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88...
February 13, 2024: EMBO Reports
https://read.qxmd.com/read/38318207/primary-cilia-in-osteoblasts-and-osteocytes-are-required-for-skeletal-development-and-mechanotransduction
#7
Mariana Moraes de Lima Perini, Julie N Pugh, Elizabeth M Scott, Karan Bhula, Austin Chirgwin, Olivia N Reul, Nicolas F Berbari, Jiliang Li
Primary cilia have been involved in the development and mechanosensation of various tissue types, including bone. In this study, we explored the mechanosensory role of primary cilia in bone growth and adaptation by examining two cilia specific genes, IFT88 and MKS5, required for proper cilia assembly and function. To analyze the role of primary cilia in osteoblasts, Osx1-GFP:Cre mice were bred with IFT88 LoxP/LoxP to generate mice with a conditional knockout of primary cilia in osteoblasts. A significant decrease in body weight was observed in both male (p=0...
December 18, 2023: bioRxiv
https://read.qxmd.com/read/38234719/the-primary-cilium-and-its-hedgehog-signaling-in-nociceptors-contribute-to-inflammatory-and-neuropathic-pain
#8
Lindsey A Fitzsimons, Larissa Staurengo-Ferrari, Oliver Bogen, Dioneia Araldi, Ivan J M Bonet, Ethan E Jordan, Jon D Levine, Kerry L Tucker
The primary cilium, a 1-3 μm long hair-like structure protruding from the surface of almost all cells in the vertebrate body, is critical for neuronal development and also functions in the adult. As the migratory neural crest settles into dorsal root ganglia (DRG) sensory neurons elaborate a single primary cilium at their soma that is maintained into adult stages. While it is not known if primary cilia are expressed in nociceptors, or their potential function in the mature DRG neuron, recent studies have shown a role for Hedgehog, whose signaling demonstrates a dependence on primary cilia, in nociceptor sensitization...
December 27, 2023: bioRxiv
https://read.qxmd.com/read/38139355/extraciliary-ofd1-is-involved-in-melanocyte-survival-through-cell-adhesion-to-ecm-via-paxillin
#9
JOURNAL ARTICLE
Nan-Hyung Kim, Chang Hoon Lee, Ai-Young Lee
Primary cilia play a significant role in influencing cell fate, including apoptosis in multiple cell types. In the lesional epidermis of vitiligo patients, a reduced number of ciliated cells was observed. Our study also revealed a downregulation of oral-facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients. However, it remains unknown whether primary cilia are involved in the control of melanocyte apoptosis. While both intraflagellar transport 88 (IFT88) and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) are associated with ciliogenesis in melanocytes, only the knockdown of OFD1 , but not IFT88 and RPGRIP1L , resulted in increased melanocyte apoptosis...
December 15, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38052491/anks1a-deficiency-aberrantly-increases-the-entry-of-the-protein-transport-machinery-into-the-ependymal-cilia
#10
JOURNAL ARTICLE
Haeryung Lee, Jiyeon Lee, Miram Shin, Soochul Park
In this study, we examine whether a change in the protein levels for FOP in Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A)-deficient ependymal cells affects the intraflagellar transport (IFT) protein transport system in the multicilia. Three distinct abnormalities are observed in the multicilia of ANKS1A-deficient ependymal cells. First, there were a greater number of IFT88-positive trains along the cilia from ANKS1A deficiency. The results are similar to each isolated cilium as well. Second, each isolated cilium contains a significant increase in the number of extracellular vesicles (ECVs) due to the lack of ANKS1A...
December 31, 2023: Molecules and Cells
https://read.qxmd.com/read/38038747/ccdc146-is-required-for-sperm-flagellum-biogenesis-and-male-fertility-in-mice
#11
JOURNAL ARTICLE
Yanjie Ma, Bingbing Wu, Yinghong Chen, Shuang Ma, Liying Wang, Tingting Han, Xiaolei Lin, Fulin Yang, Chao Liu, Jianguo Zhao, Wei Li
Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females...
December 1, 2023: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38028541/brain-microvascular-endothelial-cells-possess-a-second-cilium-that-arises-from-the-daughter-centriole
#12
JOURNAL ARTICLE
Karthikeyan Thirugnanam, Ankan Gupta, Francisco Nunez, Shubhangi Prabhudesai, Amy Y Pan, Surya M Nauli, Ramani Ramchandran
Primary cilia from the brain microvascular endothelial cells (ECs) are specialized cell-surface organelles involved in mediating sensory perception, cell signaling, and vascular stability. Immunofluorescence (IF) analysis of human primary brain microvascular ECs reveals two cilia per cell. To confirm the in vitro observation of the two-cilia phenotype in human primary brain ECs, ECs isolated from mouse brain were cultured and stained for cilium. Indeed, brain ECs from a ciliopathic mouse (polycystic kidney disease or Pkd2 -/- ) also possess more than one cilium...
2023: Frontiers in Molecular Biosciences
https://read.qxmd.com/read/38009273/primary-cilium-participates-in-radiation-induced-bystander-effects-through-tgf-%C3%AE-1-signaling
#13
JOURNAL ARTICLE
Pei Qu, Zhiang Shao, Yanan Zhang, Jinpeng He, Dong Lu, Wenjun Wei, Junrui Hua, Wei Wang, Jufang Wang, Nan Ding
Many studies have indicated that tumor growth factor-beta (TGF-β) signaling mediates radiation-induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF-β signaling to regulate diverse cellular processes. But whether the PC participates in TGF-β induced RIBEs remains unclear. The cellular levels of TGF-β1 were detected by western blot analysis and the secretion of TGF-β1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining...
November 27, 2023: Journal of Cellular Physiology
https://read.qxmd.com/read/38001823/oxidative-stress-induces-skin-pigmentation-in-melasma-by-inhibiting-hedgehog-signaling
#14
JOURNAL ARTICLE
Nan-Hyung Kim, Ai-Young Lee
There is growing evidence that oxidative stress plays a role in melasma and disrupts primary cilia formation. Additionally, primary cilia have been suggested to have an inhibitory role in melanogenesis. This study examined the potential link between oxidative stress, skin hyperpigmentation, and primary cilia. We compared the expression levels of the nuclear factor E2-related factor 2 (NRF2), intraflagellar transport 88 (IFT88), and glioma-associated oncogene homologs (GLIs) in skin samples from patients with melasma, both in affected and unaffected areas...
November 6, 2023: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/37989409/the-braf-v600e-mutation-maintains-the-aggressiveness-of-papillary-thyroid-cancers-requiring-downregulation-of-primary-cilia
#15
JOURNAL ARTICLE
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Dídac Mauricio, Song-Bo Fu
Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E -driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E -driven PTCs and that loss of cilia may be associated with lymph node metastasis...
November 19, 2023: Molecular and Cellular Endocrinology
https://read.qxmd.com/read/37967351/a-novel-primary-cilium-mediated-mechanism-through-which-osteocytes-regulate-metastatic-behavior-of-both-breast-and-prostate-cancer-cells
#16
JOURNAL ARTICLE
Stefaan W Verbruggen, Joanne Nolan, Michael P Duffy, Oliver M T Pearce, Christopher R Jacobs, Martin M Knight
Bone metastases are a common cause of suffering in breast and prostate cancer patients, however, the interaction between bone cells and cancer cells is poorly understood. Using a series of co-culture, conditioned media, human cancer spheroid, and organ-on-a-chip experiments, this study reveals that osteocytes suppress cancer cell proliferation and increase migration via tumor necrosis factor alpha (TNF-α) secretion. This action is regulated by osteocyte primary cilia and associated intraflagellar transport protein 88 (IFT88)...
November 15, 2023: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/37942288/primary-cilia-mediated-regulation-of-microglial-secretion-in-alzheimer-s-disease
#17
JOURNAL ARTICLE
Seungun Yeo, Jaemyung Jang, Hyun Jin Jung, Hyeyoung Lee, Youngshik Choe
Alzheimer's disease (AD) is a brain disorder manifested by a gradual decline in cognitive function due to the accumulation of extracellular amyloid plaques, disruptions in neuronal substance transport, and the degeneration of neurons. In affected neurons, incomplete clearance of toxic proteins by neighboring microglia leads to irreversible brain inflammation, for which cellular signaling is poorly understood. Through single-cell transcriptomic analysis, we discovered distinct regional differences in the ability of microglia to clear damaged neurites...
2023: Frontiers in Molecular Biosciences
https://read.qxmd.com/read/37875118/minibar-garre1-is-a-dual-rac-and-rab-effector-required-for-ciliogenesis
#18
JOURNAL ARTICLE
Murielle P Serres, Ronan Shaughnessy, Sophie Escot, Hussein Hammich, Frédérique Cuvelier, Audrey Salles, Murielle Rocancourt, Quentin Verdon, Anne-Lise Gaffuri, Yannick Sourigues, Gilles Malherbe, Leonid Velikovsky, Florian Chardon, Nathalie Sassoon, Jean-Yves Tinevez, Isabelle Callebaut, Etienne Formstecher, Anne Houdusse, Nicolas B David, Olena Pylypenko, Arnaud Echard
Cilia protrude from the cell surface and play critical roles in intracellular signaling, environmental sensing, and development. Reduced actin-dependent contractility and intracellular trafficking are both required for ciliogenesis, but little is known about how these processes are coordinated. Here, we identified a Rac1- and Rab35-binding protein with a truncated BAR (Bin/amphiphysin/Rvs) domain that we named MiniBAR (also known as KIAA0355/GARRE1), which plays a key role in ciliogenesis. MiniBAR colocalizes with Rac1 and Rab35 at the plasma membrane and on intracellular vesicles trafficking to the ciliary base and exhibits fast pulses at the ciliary membrane...
October 20, 2023: Developmental Cell
https://read.qxmd.com/read/37858465/primary-cilia-control-oligodendrocyte-precursor-cell-proliferation-in-white-matter-injury-via-hedgehog-independent-creb-signaling
#19
JOURNAL ARTICLE
Kimberly K Hoi, Wenlong Xia, Ming Ming Wei, Maria Jose Ulloa Navas, Jose-Manuel Garcia Verdugo, Maxence V Nachury, Jeremy F Reiter, Stephen P J Fancy
Remyelination after white matter injury (WMI) often fails in diseases such as multiple sclerosis because of improper recruitment and repopulation of oligodendrocyte precursor cells (OPCs) in lesions. How OPCs elicit specific intracellular programs in response to a chemically and mechanically diverse environment to properly regenerate myelin remains unclear. OPCs construct primary cilia, specialized signaling compartments that transduce Hedgehog (Hh) and G-protein-coupled receptor (GPCR) signals. We investigated the role of primary cilia in the OPC response to WMI...
October 17, 2023: Cell Reports
https://read.qxmd.com/read/37830570/increasing-ciliary-arl13b-expression-drives-active-and-inhibitor-resistant-smoothened-and-gli-into-glioma-primary-cilia
#20
JOURNAL ARTICLE
Ping Shi, Jia Tian, Julianne C Mallinger, Dahao Ling, Loic P Deleyrolle, Jeremy C McIntyre, Tamara Caspary, Joshua J Breunig, Matthew R Sarkisian
ADP-ribosylation factor-like protein 13B (ARL13B), a regulatory GTPase and guanine exchange factor (GEF), enriches in primary cilia and promotes tumorigenesis in part by regulating Smoothened (SMO), GLI, and Sonic Hedgehog (SHH) signaling. Gliomas with increased ARL13B , SMO , and GLI2 expression are more aggressive, but the relationship to cilia is unclear. Previous studies have showed that increasing ARL13B in glioblastoma cells promoted ciliary SMO accumulation, independent of exogenous SHH addition. Here, we show that SMO accumulation is due to increased ciliary, but not extraciliary, ARL13B...
September 26, 2023: Cells
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