TY - JOUR. T1 - The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. AU - Liem, Karel F.. AU - Ashe, Alyson. AU - He, Mu. AU - Satir, Peter. AU - Moran, Jennifer. AU - Beier, David. AU - Wicking, Carol. AU - Anderson, Kathryn V.. PY - 2012/6/11. Y1 - 2012/6/11. N2 - Two intraflagellar transport (IFT) complexes, IFT-A and IFT-B, build and maintain primary cilia and are required for activity of the Sonic hedgehog (Shh) pathway. A weak allele of the IFT-A gene, Ift144, caused subtle defects in cilia structure and ectopic activation of the Shh pathway. In contrast, strong loss of IFT-A, caused by either absence of Ift144 or mutations in two IFT-A genes, blocked normal ciliogenesis and decreased Shh signaling. In strong IFT-A mutants, the Shh pathway proteins Gli2, Sufu, and Kif7 localized correctly to cilia tips, suggesting that these pathway components were trafficked by IFT-B. In contrast, the membrane proteins Arl13b, ACIII, and Smo failed to ...
Polycystic kidney disease is characterized by cardiovascular irregularities, including hypertension. Dopamine, a circulating hormone, is implicated in essential hypertension in humans and animal models. Vascular endothelial primary cilia are known to function as mechano-sensory organelles. Although both primary cilia and dopamine receptors play important roles in vascular hypertension, their relationship has never been explored. To determine the roles of the dopaminergic system and mechano-sensory cilia, we studied the effects of dopamine on ciliary length and function in wild-type and mechano-insensitive polycystic mutant cells (Pkd1−/− and Tg737orpk/orpk). We show for the first time that mouse vascular endothelia exhibit dopamine receptor-type 5 (DR5), which colocalizes to primary cilia in cultured cells and mouse arteries in vivo. DR5 activation increases cilia length in arteries and endothelial cells through cofilin and actin polymerization. DR5 activation also restores cilia function in ...
3-OST-5 controls cilia length through a pathway that controls the expression of two ciliogenic transcription factor genes in KV, foxj1a and rfx2, and the FGF response gene sef. Fgfr1 and 3-OST-5 have similar functions: they regulate DFC/KV expression of foxj1a and rfx2, cilia length and asymmetric fluid flow in KV, and are cell-autonomously required in KV cells for LR development (Neugebauer et al., 2009). In addition, they have similar phenotypes, such as curved body axis, that are common in morphants or mutants of ciliogenic genes such as polaris (ift88) and foxj1a (Bisgrove et al., 2005; Yu et al., 2008; Tian et al., 2009; Hellman et al., 2010). Thus, it is likely that 3-OST-5 and Fgfr1 signaling function in the same ciliogenic pathway to regulate LR development; this is further substantiated by dosage experiments with 3-OST-5 and the Fgf8 ligand (Fig. 3). We propose that 3-OST-5 in DFC/KV cells generates a glycocode necessary for FGF signaling at the cell surface, which then maintains the ...
Cilia are microtubule-based organelles that are expressed on the surface of most cells in the mammalian body. Intraflagellar transport (IFT), the process by which cilia are formed and maintained, was first described in Chlamydomonas, and proteins required for IFT concentrate at the base of cilia, where they assemble into large protein complexes called IFT particles (Kozminski et al., 1995; Piperno and Mead, 1997). The IFT particles are trafficked along the axoneme by a heterotrimeric kinesin-II and a cytoplasmic dynein in the anterograde and retrograde directions, respectively. Cilia and flagella have diverse functions ranging from fluid and cell movement to mechanosensation and sensory perception (Davenport and Yoder, 2005; Scholey, 2003).. In mammals, Kif3a is a component of the kinesin-II motor protein complex required for cilia assembly while Ift88 (also known as Tg737 or polaris) is a core component of the IFT particle (Cole et al., 1998; Pazour et al., 2000; Taulman et al., 2001). Mice ...
Purpose : Primary cilia are hair-like organelles that extend from the apical surface of most mammalian cells. Defects in primary cilia in the eye cause ciliopathies, including renal disease, cerebral anomalies and retinitis pigmentosa. Currently, it is well-known that the connecting cilium in rod and cone photoreceptors contribute to phototransduction. However, the role of cilia in non-photoreceptors in the retina remains unknown. The purpose of this study is to describe the distribution of primary cilia in other layers of retina in mouse and human during development. Methods : In this study, eyes were collected from the different developmental stages in Centrin2-GFP::Arl13b-mCherry transgenic mice, wildtype CD1 mice and C57BL/6J mice to study the distribution of primary cilia in vivo. Retinal sections were stained using Pax6, Sox9, and Chx10 antibodies to determine the fraction of ciliated cells that express these markers. In addition, wildtype CD1 and C57BL/6J mice eyes were used for whole ...
TY - JOUR. T1 - Sensory Signaling-Dependent Remodeling of Olfactory Cilia Architecture in C. elegans. AU - Mukhopadhyay, Saikat. AU - Lu, Yun. AU - Shaham, Shai. AU - Sengupta, Piali. PY - 2008/5/13. Y1 - 2008/5/13. N2 - Nonmotile primary cilia are sensory organelles composed of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis, and signaling protein targeting and localization via as yet poorly understood mechanisms. Here, we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory signaling results in alteration of axoneme length and expansion of a membraneous structure, thereby altering the topological distribution of a subset of ciliary transmembrane signaling molecules. Signaling-regulated alteration of ciliary structures can be bypassed by modulation of ...
Adipose-derived stem cells (ASC) are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC) differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1), polycystin-2 (PC2) and intraflagellar transport protein-88 (IFT88), in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the
Description: Glial cells maintain homeostasis that is essential to neuronal function. Injury to the nervous system leads to the activation and proliferation of glial cells and pericytes, which helps to wall off the damaged region and restore homeostatic conditions. Sonic hedgehog is a mitogen which is implicated in injury-induced proliferation of glial cells and pericytes. The mitogenic effects of sonic hedgehog require primary cilia, but the few reports on glial or pericyte primary cilia do not agree about their abundance and did not address effects of injury on these cilia. Primary cilia are microtubule-based organelles that arise from the centrosome and are retracted before cells divide. Depending on cell type, proteins concentrated in cilia can transduce several mitotic, chemosensory, or mechanosensory stimuli. The present study investigated effects of stab wound injury on the incidence and length of glial and pericyte primary cilia in the area adjacent to the injury core. Astrocytes, ...
We have characterized the adenylyl cyclase activity in a newly developed preparation of isolated olfactory cilia from the bovine chemosensory neuroepithelium. Like its counterparts from frog and rat, the ciliary enzyme was stimulated by guanine nucleotides, by forskolin, and by a variety of odorants in the presence of GTP. The main difference between the bovine olfactory cilia preparation and the frog and rat olfactory cilia preparation is that odorant stimulation of the bovine olfactory adenylyl cyclase is strongly inhibited by submillimolar concentrations of dithiothreitol. This inhibition is a consequence of a concomitant increase in the GTP-stimulated level and the decrease of the odorant stimulation of the enzyme. Nasal respiratory cilia have a much lower level of adenylyl cyclase activity and show no odorant stimulation. Owing to the large quantities of material available, the bovine olfactory cilia preparation is advantageous for studies of the proteins involved in chemosensory
Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3β inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the ...
Primary cilia are microtubule-based organelles that extend from the surface of most vertebrate cells. Our lab showed that Hedgehog signaling in mammals depends on this organelle. We study how this organelle controls Hedgehog signaling and the mechanisms that control cilia formation
Cilia are small, microtubule-based protrusions important for development and homeostasis. We recently demonstrated that the planar cell polarity effector protein Fuz is a critical regulator of axonemal intraflagellar transport dynamics and localization. Here, we report our findings on the role of the small GTPase Rsg1, a known binding partner of Fuz, and its role in the dynamics and cytoplasmic localization of intraflagellar transport proteins. We find that Rsg1 loss of function leads to impaired axonemal IFT dynamics in multiciliated cells. We further show that Rsg1 is required for appropriate cytoplasmic localization of the retrograde IFT-A protein IFT43. Finally, we show that Rsg1 governs the apical localization of basal bodies, the anchoring structures of cilia. Our data suggest that Rsg1 is a regulator of multiple aspects of ciliogenesis, including apical trafficking of basal bodies and the localization and dynamics intraflagellar transport proteins ...
A consensus has not been reached on the mechanism for how the nodal flow induces an asymmetric signal that ultimately results in asymmetric regions of left-specific gene expression (Tabin 2006). The main theories involve asymmetric bending of mechanosensory cilia on opposite sides of the node (McGrath et al. 2003; Tabin & Vogan 2003) or the directional transport of (i) morphogen proteins (Nonaka et al. 1998) or (ii) nodal vesicular parcels (NVPs) that are vesicles containing sonic hedgehog (SHH) and retinoic acid (RA; Tanaka et al. 2005). It was also not immediately obvious how whirling cilia could produce such a directional flow. The rotating motion appears to result from bending of the cilium close to its base. Although the base of the cilium is fixed and the cilium does not rotate about its centreline, the direction of bending near the base rotates continuously. As noted by both Nonaka et al. (2005) and Okada et al. (2005), the majority of cilia are not tilted to the degree that they make ...
Lien vers Pubmed [PMID] - 21501571. Biol Aujourdhui 2011;205(1):5-28. Cilia and flagella are ubiquitous organelles that protrude from the surfaces of many cells, and whose architecture is highly conserved from protists to humans. These complex organelles, composed of over 500 proteins, can be either immotile or motile. They are involved in a myriad of biological processes, including sensing (non-motile cilia) and/or cell motility or movement of extracellular fluids (motile cilia). The ever-expanding list of human diseases linked to defective cilia illustrates the functional importance of cilia and flagella. These ciliopathies are characterised by an impressive diversity of symptoms and an often complex genetic etiology. A precise knowledge of cilia and flagella biology is thus critical to better understand these pathologies. However, multi-ciliated cells are terminally differentiated and difficult to manipulate, and a primary cilium is assembled only when the cell exits from the cell cycle. In ...
TY - JOUR. T1 - Linking early determinants and cilia-driven leftward flow in left-right axis specification of Xenopus laevis. T2 - A theoretical approach. AU - Schweickert, Axel. AU - Walentek, Peter. AU - Thumberger, Thomas. AU - Danilchik, Mike. PY - 2012/2/1. Y1 - 2012/2/1. N2 - In vertebrates, laterality - the asymmetric placement of the viscera including organs of the gastrointestinal system, heart and lungs - is under the genetic control of a conserved signaling pathway in the left lateral plate mesoderm (LPM). A key feature of this pathway, shared by embryos of all non-avian vertebrate classes analyzed to date (e.g. fish, amphibia and mammals) is the formation of a transitory midline epithelial structure. Remarkably, the motility of cilia projecting from this epithelium produce a leftward-directed movement of extracellular liquid. This leftward flow precedes any sign of asymmetry in gene expression. Numerous analyses have shown that this leftward flow is not only necessary, but indeed ...
Eukaryotic cilia and flagella are cellular structures familiar to schoolchildren everywhere for the elegant swath they cut as they propel protozoa through pond water. Less well recognized is the fact that a single immotile cilium is present on almost every type of vertebrate cell. These so-called primary cilia were discovered more than a century ago and, yet, their functions remain largely unexplored (Singla and Reiter, 2006).. It is now becoming clear that the primary cilium plays important roles in both development and disease. Perhaps its most dramatic function is in the kidney - ciliary defects cause polycystic kidney disease, the most common life-threatening monogenic illness. Primary cilia also have roles in sensing environmental information. Photoreceptors and odorant receptors function on primary cilia, and primary cilia are essential for sound reception. Therefore, it is not much of an exaggeration to say that we see, smell and hear through cilia.. Our work suggests that cilia also ...
Primary cilia are critical for Hedgehog (Hh) signaling in vertebrates, and defects in Hh signaling or cilium structure cause pleiotropic diseases known as ciliopathies in humans. Binding of a Hh ligand to the receptor Patched (Ptc) relieves Ptc-mediated inhibition of the seven-transmembrane protein Smoothened (Smo). Through a mechanism that is not entirely clear, this leads to accumulation of Smo in the cilium and subsequent recruitment of Suppressor of Fused (SuFu) and the Gli transcription factors into the cilium. The Glis are then processed into active forms that translocate into the nucleus to mediate Hh signaling outputs. Mutations in the gene encoding Ellis-van Crevid syndrome protein 2 (Evc2) cause inherited ciliopathy syndromes in which cilia of various cell types appear normal yet show impaired Hh signaling. Dorn et al. report that the cilium-localized protein Evc2 was required for Sonic hedgehog (Shh)-induced transcription of GLI1 in cultured human fibroblasts but had no function in ...
Cilia are microtubule based structures that can be motile or immotile, the latter being referred to as primary cilia. In contrast to motile cilia, such as those found on epithelia of the trachea, the importance of the primary cilium is relatively undefined despite their presence on most mammalian cells. Cilia are extremely complex organelles which are devoid of ribosomes, thus, proteins required for cilia assembly, maintenance, and signaling must be imported into the cilium. This occurs through a microtubule-based transport system called intraflagellar transport (IFT). Proteins involved in IFT concentrate around the basal body at the base of the cilium and assemble into complexes (IFT particles) which are moved up the cilium by a kinesin and returned by a cytoplasmic dynein. The IFT particle is thought to mediate the transport of cargo into the cilium as well as to deliver signals initiated in the cilium to the cytosol. Although the primary cilium was once thought to be a vestigial organelle, ...
Actin fibers and microtubules help cilia coordinate the direction and sequence of their beating, Werner et al. show.. At first, the multiple cilia on an embryonic cell are a bit like the musicians in a garage band, each doing its own thing. But over time the filaments turn so that they all beat in the same direction. They also coordinate their timing, so that the cilia at the front of the cell beat first and the ones at the back of the cell stroke last. The planar cell polarity signaling pathway and hydrodynamic forces on the cilia help set up this polarity. Using the cilia-coated epithelial cells of Xenopus embryos, Werner et al. investigated the roles of the actin and microtubule cytoskeletons in the process.. Werner et al. observed actin fibers connecting neighboring cilia. These filaments were absent in the youngest cells that hadnt yet polarized. To determine the fibers function, the researchers disassembled them using the drug cytochalasin D. Without actin fibers, the cilia couldnt ...
In the kidney, primary cilia extend off the apical surface of the epithelium into the tubule lumen and are present on most cells of the nephron (Figure 1B). These cilia were thought to be of minimal importance for renal development. However, several studies in model organisms, some of which paradoxically lack kidneys, led to an increase in clinical and basic research directed at understanding the function of the renal cilium (reviewed in references [2,6,7]).. In one of these studies, Barr and Sternberg (46) revealed that the homologs of polycystin-1 and -2, which are involved in the dominant forms of PKD (ADPKD) in humans, localize to cilia of sensory neurons of C. elegans. This has also been shown for the human and mouse homologs (35,47). Loss of the polycystins in C. elegans did not disrupt cilia formation but rather altered behavioral responses that require cilia function. At approximately the same time, several groups that were working in Chlamydomonas, C. elegans, and mice uncovered that ...
Cilia are conserved organelles that have important motility, sensory and signalling roles. The transition zone (TZ) at the base of the cilium is critical for cilia function, and defects in several TZ proteins are associated with human congenital ciliopathies such as Nephronophthisis (NPHP) and Meckel Gruber syndrome (MKS). In several species, MKS and NPHP proteins form separate complexes that cooperate with Cep290 to assemble the TZ, but flies appear to lack core components of the NPHP module. We show that MKS proteins in flies are spatially separated from Cep290 at the TZ, and that flies mutant for individual MKS genes fail to recruit other MKS proteins to the TZ, while Cep290 appears to be recruited normally. Although there are abnormalities in microtubule and membrane organisation in developing MKS mutant cilia, these defects are less apparent in adults, where sensory cilia and sperm flagella appear to function quite normally. Thus, localising MKS proteins to the cilium or flagellum is not ...
This paper introduces a new design for individually controlled magnetic artificial cilia for use in fluid devices and specifically intended to improve the mixing in DNA microarray experiments. The design has been implemented using a low-cost prototype that can be fabricated using polydimethylsiloxane (PDMS) and off-the-shelf parts and achieves large cilium deflections (59% of the cilium length). The devices performance is measured via a series of mixing experiments using different actuation patterns inspired by the blinking vortex theory. The experimental results, quantified using the relative standard deviation of the color when mixing two colored inks, show that exploiting the individual control leads to faster mixing (38% reduction in mixing time) than when operating the device in a simultaneous-actuation mode with the same average cilium beat frequency. Furthermore, the experimental results show an optimal beating pattern that minimizes the mixing time. The existence and character of this ...
Cilia and flagella are microtubule-based organelles present at the surface of most cells, ranging from protozoa to vertebrates, in which they are implicated in processes from morphogenesis to cell motility. In vertebrate neurons, microtubule-associated MAP6 proteins stabilize cold-resistant microtubules via their Mn and Mc modules, and play a role in synaptic plasticity. Although centrioles, cilia and flagella have cold-stable microtubules, MAP6 proteins have not been identified in these organelles, suggesting that additional proteins support this role in these structures. Here, we characterize HsSAXO1 (FAM154A) as the first human member of a widely conserved family of MAP6-related proteins specific to centrioles and cilia microtubules. Our data demonstrated that HsSAXO1 binds specifically to centriole and cilia microtubules. We identify, in vivo and in vitro, HsSAXO1 Mn modules as responsible for microtubule binding and stabilization as well as being necessary for cilia localization. Finally, ...
Investigator: Grant Turner. Mentor: Joseph Sisson, MD. Cilia are essential components of multiple organ systems. Inherited defects in ciliogenesis, the formation of cilia, are often lethal in utero, indicating a critical role for cilia in growth and development. Intraflagellar transport proteins (IFTs) are a diverse group of proteins that are essential for moving proteins on and off of the axoneme and found to have multiple important functions in the structure and function of cilia. For example, defects in IFT88 cause severe defects in the sensing cilia in the kidneys, resulting in polycystic kidney formation, and in the lung, where bronchiectasis results. While the role of IFTs in ciliogenesis has been established, the specific role IFT88 plays in airway cilia structure and function is unknown. We hypothesized that: 1) IFT88 is required for de novo ciliogenesis in vitro; and 2) IFT88 is required to translocate the methacholine receptor, which is part of a cilia motility regulator complex, from ...
Recent studies of the primary cilium have begun to provide further insights into ciliary ultrastructure, with an emerging picture of complex compartmentalization and molecular components that combine in functional modules. Many proteins that are mutated in ciliopathies are localized to the transition zone, a compartment of the proximal region of the cilium. The loss of these components can disrupt ciliary functions such as the control of protein entry and exit from the cilium, the possible trafficking of essential ciliary components, and the regulation of signaling cascades and control of the cell cycle. The discovery of functional modules within the primary cilium may help in understanding the variable phenotypes and pleiotropy in ciliopathies.
TY - JOUR. T1 - Mechanism of transport of IFT particles in C. elegans cilia by the concerted action of kinesin-II and OSM-3 motors. AU - Pan, Xiaoyu. AU - Ou, Guangshuo. AU - Civelekoglu-Scholey, Gul. AU - Blacque, Oliver E.. AU - Endres, Nicholas F.. AU - Tao, Li. AU - Mogilner, Alex. AU - Leroux, Michel R.. AU - Vale, Ronald D.. AU - Scholey, Jonathan M.. PY - 2006/9/25. Y1 - 2006/9/25. N2 - The assembly and function of cilia on Caenorhabditis elegans neurons depends on the action of two kinesin-2 motors, heterotrimeric kinesin-II and homodimeric OSM-3-kinesin, which cooperate to move the same intraflagellar transport (IFT) particles along microtubule (MT) doublets. Using competitive in vitro MT gliding assays, we show that purified kinesin-II and OSM-3 cooperate to generate movement similar to that seen along the cilium in the absence of any additional regulatory factors. Quantitative modeling suggests that this could reflect an alternating action mechanism, in which the motors take turns to ...
ginkgo --focus=Runtime* -noColor -v -dryRun Running Suite: runtime ====================== Random Seed: 1516125117 Will run 42 of 164 specs ................ RuntimePolicyEnforcement Policy Enforcement Always Always to Never with policy /Users/ianvernon/go/src/github.com/cilium/cilium/test/runtime/Policies.go:258 • ------------------------------ RuntimePolicyEnforcement Policy Enforcement Always Always to Never without policy /Users/ianvernon/go/src/github.com/cilium/cilium/test/runtime/Policies.go:293 • ------------------------------ RuntimePolicyEnforcement Policy Enforcement Never Container creation /Users/ianvernon/go/src/github.com/cilium/cilium/test/runtime/Policies.go:332 • ------------------------------ RuntimePolicyEnforcement Policy Enforcement Never Never to default with policy /Users/ianvernon/go/src/github.com/cilium/cilium/test/runtime/Policies.go:349 ................. Ran 42 of 164 Specs in 0.002 seconds SUCCESS! -- 0 Passed , 0 Failed , 0 Pending , 122 Skipped PASS Ginkgo ...
kubectl -n kube-system get pods -l k8s-app=cilium NAME READY STATUS RESTARTS AGE cilium-5ngzd 1/1 Running 0 3m19s $ kubectl -n kube-system exec cilium-1c2cz -- cilium endpoint list ENDPOINT POLICY (ingress) POLICY (egress) IDENTITY LABELS (source:key[=value]) IPv6 IPv4 STATUS ENFORCEMENT ENFORCEMENT 108 Disabled Disabled 104 k8s:io.cilium.k8s.policy.cluster=default 10.15.233.139 ready k8s:io.cilium.k8s.policy.serviceaccount=coredns k8s:io.kubernetes.pod.namespace=kube-system k8s:k8s-app=kube-dns 1011 Disabled Disabled 104 k8s:io.cilium.k8s.policy.cluster=default 10.15.96.117 ready k8s:io.cilium.k8s.policy.serviceaccount=coredns k8s:io.kubernetes.pod.namespace=kube-system k8s:k8s-app=kube-dns 2407 Disabled Disabled 22839 k8s:class=deathstar 10.15.129.95 ready k8s:io.cilium.k8s.policy.cluster=default k8s:io.cilium.k8s.policy.serviceaccount=default k8s:io.kubernetes.pod.namespace=default k8s:org=empire 2607 Disabled Disabled 4 reserved:health 10.15.28.196 ready 3339 Disabled Disabled 22839 ...
The breaking of left-right symmetry in the mammalian embryo is believed to occur in a transient embryonic structure, the node, when cilia create a leftward flow of liquid. It has been widely confirmed that this nodal flow is the first sign of left-right differentiation; however, the mechanism through which embryonic cilia produce their movement and how the leftward flow confers laterality are still requiring investigation. The ciliary motility in the embryonic node involves complex dynein activations and the handed information is transmitted to the cells by the flow produced by cilia, either mechanically and/or by advection of a chemical species. In this paper, we present a computational model of ciliary ultrastructure (protein-structure model) and discuss the scenarios that incorporate this internal microtubule-dynein system with the external fluidic environment (fluid-structure-protein interaction model, FSPI). By employing computational fluid dynamics, deformable mesh computational techniques ...
Primary cilia are microtubule-based organelles that extend from the surface of most vertebrate cells. Our lab showed that Hedgehog signaling in mammals depends on this organelle. We study how this organelle controls Hedgehog signaling and the mechanisms that control cilia formation. ...
Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of technical limitations and the specific structural and functional modifications that cannot be modeled in vitro. With recent advances in microscopy techniques and molecular and biochemical approaches, we are now beginning to understand the molecular basis of photoreceptor ciliary architecture, ciliary function and its involvement in human diseases. Here, I will discuss the studies that have revealed new knowledge of how photoreceptor cilia regulate their identity and function while coping with high metabolic and trafficking demands associated with processing light signal.
The ctenophore swimming-plate has been examined with the electron microscope. It has been recognized as an association of long cilia in tight hexagonal packing. One of the directions of the hexagonal packing is parallel to the long edge of the swimming-plate and is perpendicular to the direction of the ciliary beat. All the cilia in the swimming-plate are identically oriented. The effective beat in the movement of the swimming-plate is directed towards the aboral pole of the animal, and this is also the side of the unpaired peripheral filament in all the cilia. The direction of the ciliary beat is fixed in relation to the position of the filaments of the cilia. The swimming-plate cilium differs from other types of cilia and flagella in having a filament arrangement that can be described as 9 + 3 as opposed to the conventional 9 + 2 pattern. The central filaments appear in a group of two "tubular" filaments and an associated compact filament. The compact filament might have a supporting function. ...
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We are happy to welcome you to the 10th Meeting on Cilia, Flagella and Centrosomes, held from the 10th to the 12th of October 2017 at the Séminaire Le Saint Paul (http://lesaintpaul-hotel.fr/).. The CFC conference is a biennial meeting organized in alternation with the European Cilia meeting to bring together around 80 participants working on the biology of cilia, flagella and centrosomes in France and all over Europe. It is an excellent place for lively exchanges between researchers at all stages of their career, from internationally renowned keynote speakers to early stage students.. http://univ-cotedazur.fr/events/cfc2017. ...
The individual role of the outer dynein arm light chains in the molecular mechanisms of ciliary movements in response to second messengers, such as Ca(2+) and cyclic nucleotides, is unclear. We examined the role of the gene termed the outer dynein arm light chain 1 (LC1) gene of Paramecium tetraurelia (ODAL1), a homologue of the outer dynein arm LC1 gene of Chlamydomonas reinhardtii, in ciliary movements by RNA interference (RNAi) using a feeding method. The ODAL1-silenced (ODAL1-RNAi) cells swam slowly, and their swimming velocity did not increase in response to membrane-hyperpolarizing stimuli. Ciliary movements on the cortical sheets of ODAL1-RNAi cells revealed that the ciliary beat frequency was significantly lower than that of control cells in the presence of ≥ 1 mM Mg(2+)-ATP. In addition, the ciliary orientation of ODAL1-RNAi cells did not change in response to cyclic AMP (cAMP). A 29-kDa protein phosphorylated in a cAMP-dependent manner in the control cells disappeared in the axoneme ...
Interface to be used when running Cilium on top of a CNI plugin. # For flannel, use cni0 flannel-master-device: cni0 # When running Cilium with policy enforcement enabled on top of a CNI plugin # the BPF programs will be installed on the network interface specified in # flannel-master-device and on all network interfaces belonging to # a container. When the Cilium DaemonSet is removed, the BPF programs will # be kept in the interfaces unless this option is set to true. flannel-uninstall-on-exit: false # Installs a BPF program to allow for policy enforcement in already running # containers managed by Flannel. # NOTE: This requires Cilium DaemonSet to be running in the hostPID. # To run in this mode in Kubernetes change the value of the hostPID from # false to true. Can be found under the path `spec.spec.hostPID` flannel-manage-existing-containers: false ...
A screening platform was developed by culturing cancer cells in a 96-well plates followed by immunostaining for cilia. Quantification of cilia was accomplished by analyzing images captured by INCell Analyzer, an automated machine used for image acquisition. Ciliogenic compounds were identified based on percentage of ciliated cells. The hits were further assessed in cancer cells. Their ability to decrease the proliferation of cancer cells was analyzed by spheroid assay. Western Blots were performed to identify the pathways through which ciliogenesis was induced by these compounds. ...
Across the animal and plant kingdom, motile cilia and flagella serve many important biological functions, including cellular propulsion, fluid transport, and sensory signaling - to name only a few. Unraveling the physiology of these integral cell organelles is an interdisciplinary endeavor at the interface of physics and biology. This research field involves studies of ciliary structure, self-organized dynamics of the ciliary beat, collective dynamics at the cellular and multicellular level, and the pathophysiology of impaired cilia function in ciliopathies. The aim of this seminar is to bring together scientists from different disciplines to address the physical, biological, and medical aspects of motile cilia.. The main topics of the seminar are:. ...
Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332). Required for the correct localization of ciliary and phototransduction proteins in retinal photoreceptor cells; may play a role in ciliary transport processes (By similarity). Required for efficient recruitment of RAB8A to primary cilium (PubMed:17705300). In the ciliary transition zone is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involved in regulation of the BBSome complex integrity, specifically for ...
Recent studies in several organisms have contributed to an effort to amalgamate a complete list of ciliary proteins, or ciliome. Comparative genomic studies were performed in Chlamydomonas (Li et al., 2004) and Drosophila (Avidor-Reiss et al., 2004), taking advantage of the fact that subtracting the genomes of ciliated organisms (including C. elegans) from those lacking cilia (e.g., Arabidopsis thaliana) provides considerable enrichment for ciliary genes. Other more direct approaches aimed at identifying ciliary proteins, in the form of proteomic analyses, were performed using Chlamydomonas (Pazour et al., 2005), human airway cells (Ostrowski et al., 2002), Tetrahymena (Smith et al., 2005) and Trypanosoma brucei (Broadhead et al., 2006). Of note, all of the above studies were accomplished using experimental systems or cells that possess motile cilia (with the exception of Drosophila, which also has non-motile cilia). Helping to address this shortfall, C. elegans has been used to assemble a ...
Abnormal Hedgehog (Hh) pathway activity has been reported in many cancers including basal cell carcinomas, medulloblastomas, rhabdomyosarcomas, glioblastomas, breast and prostate cancers. For this reason the Hh pathway is a flourishing area for development of anti-cancer drugs such as Hh ligand antagonists (e.g. 5E1, robotnikinin), Smo inhibitors (e.g. GDC-0449, IPI-926) and Gli transcriptional activity inhibitors (e.g. GANT58, GANT61). In vertebrate cells it is now clear that primary cilia are required for activation of the Hh pathway in normal cells. It is in the primary cilium that both positive and negative effectors of the Hh pathway are processed by post-translational modifications. In many cancers, preliminary results suggest that primary cilia are lost. As drugs are developed that inhibit different steps of the Hh pathway, it is important to consider how these drugs will function in the context of primary cilia in the tumor environment. We will discuss why some of the Hh inhibitors may ...
Cilia are specialized, hair-like structures that project from the cell bodies of eukaryotic cells. With increased understanding of the distribution and functions of various types of cilia, interest in these organelles is accelerating. To effectively use this great expansion in knowledge, this information must be made digitally accessible and available for large-scale analytical and computational investigation. Capture and integration of knowledge about cilia into existing knowledge bases, thus providing the ability to improve comparative genomic data analysis, is the objective of this work. We focused on the capture of information about cilia as studied in the laboratory mouse, a primary model of human biology. The workflow developed establishes a standard for capture of comparative functional data relevant to human biology. We established the 310 closest mouse orthologs of the 302 human genes defined in the SYSCILIA Gold Standard set of ciliary genes. For the mouse genes, we identified biomedical
The UK Cilia Network brings together researchers working on various aspects of cilia structure and function in a broad range of cell and tissue types. This multidisciplinary group aims to foster collaboration and sharing of expertise in order to further understanding of this fascinating organelle and its role in development, ageing, health and disease.
Pcnt interacts with proteins involved in cilia assembly and function. (a) Pooled IFT fractions from a sucrose gradient from mouse testes were applied to an FPLC
Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic ...
ATTENTION ALL CELL BIOLOGISTS !!!!! NOW HEAR THIS !! I AM A MEDICAL RESEARCHER IN NEW ZEALAND. I AM INVESTIGATING POSSIBLE ROLES OF PRIMARY CILIA USING CONFOCAL LASER MICROSCOPY WITH ANTIBODY LABELLING. IF YOU HAVE ANY HYPOTHESES REGARDING PRIMARY CILIA FUNCTION I WOULD LOVE TO HEAR THEM. REGARDS, GEORGE ...
Just published in the Journal of Cell Biology is a paper from Dr. Suzanna Prosser and Ciaran Morrison on how cells regulate the formation of primary cilia, antenna-like sensory structures that extend from the cell surface to respond to various extracellular signals.. http://jcb.rupress.org/content/early/2015/03/03/jcb.201411070.full. http://www.nuigalway.ie/about-us/news-and-events/news-archive/2015/march2015/antenna-like-structures-found-on-immune-cells-for-first-time.html. ...
Primary cilia on renal tubular epithelial cells sense fluid flow and help maintain cell structure and function. Deletion, malformation, or loss of function of the cilium results in renal cyst formation, as seen in PKD. While embryonic deletion of cilia or cystoproteins is lethal or causes massive cyst formation, deletion of cilia or cystoproteins in the adult mouse does not lead to significant cyst formation for months (9, 21, 27, 29). This delay in cystogenesis has provided a model that can be used to study factors or conditions that can modify the initiation and rate of cystogenesis. This is important, since there is a lack of understanding regarding factors that influence the rate of cystogenesis.. Recently, we reported that nephrectomy-induced renal hypertrophy dramatically increased the initiation and rate of cystic disease in the absence of cilia (3). Additionally, we found that, in the absence of cilia, reduced renal mass led to a significant increase in structural and functional ...
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function. Although ciliopathies are usually considered to involve proteins that localize to motile and/or immotile (primary) cilia or centrosomes, it is possible for ciliopathies to be associated with proteins such as XPNPEP3, which localizes to mitochondria but is believed to affect ciliary function through proteolytic cleavage of ciliary proteins. Significant advances in understanding the importance of cilia were made beginning in the mid-1990s. However, the physiological role that this organelle plays in most tissues remains elusive. Additional studies of how ciliary dysfunction can lead to such severe disease and developmental pathologies is a subject of current research. A wide variety of symptoms are potential clinical features of ciliopathy. Chemosensation abnormalities, typically via ciliated epithelial cellular dysfunction. Defective thermosensation or ...
Background: Recent research into ciliary structure and function provides important insights into inherited diseases termed ciliopathies and other cilia-related disorders. This wealth of knowledge needs to be translated into a computational representation to be fully exploitable by the research community. To this end, members of the Gene Ontology (GO) and SYSCILIA Consortia have worked together to improve representation of ciliary substructures and processes in GO. Methods: Members of the SYSCILIA and Gene Ontology Consortia suggested additions and changes to GO, to reflect new knowledge in the field. The project initially aimed to improve coverage of ciliary parts, and was then broadened to cilia-related biological processes. Discussions were documented in a public tracker. We engaged the broader cilia community via direct consultation and by referring to the literature. Ontology updates were implemented via ontology editing tools. Results: So far, we have created or modified 127 GO terms representing