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PubMed2003

Making human nasal cilia beat in the cold: a real time assay for cell signalling.

Human nasal epithelium must adapt to cold climates, and yet, in vitro, human ciliary beat frequency (CBF) is zero at 4 degrees C. Similarly, hibernating mammals do not die of pneumonia despite a core body temperature as low as 6 degrees C, implying that cilia continue to beat. Here, we show that protein kinase C (PKC) and Ca(2+)/calmodulin-dependent kinase II (CaMKII) regulate the profile of human nasal CBF in response to rising temperature from 4 degrees C. Onset of ciliary beat was at 10 degrees C in Medium 199, 7 degrees C in the presence of the PKC activator phorbol 12-myristate 13-acetate (PMA), the calcium ionophore ionomycin, or the CAMKII blocker myristoylated autocamtide-2 related inhibitory peptide (MACI), and 6 degrees C for the myristoylated peptide PKC inhibitor EGF-R Fragment 651-658 (MyrPKCI). During cell warming to 32 degrees C, the thermal profile was sigmoid in all solutions except those containing MACI+PMA. Surprisingly, cilia continued to beat despite 4 degrees C and were significantly more responsive to rising temperature with either MACI+PMA, or MACI+MyrPKCI. Our data suggest that CaMKII and PKC regulate the thermal slope and profile of CBF in vitro, and that when these protein kinases are manipulated, cilia can continue to beat despite hypothermia. These findings may relate to adaptive responses to cold climates.

Adaptation, Physiological↗
PubMed1977

Major membrane protein differences in cilia and flagella: evidence for a membrane-associated tubulin.

The membrane of both sperm flagella and gill cilia of the scallop Aequipecten irradians may be selectively solubilized in 1% Triton X-100, 30 mM tris(hydroxymethyl)-aminomethane hydrochloride (Tris-HCl), pH8, and 3 mM MgCl2, leaving the axoneme totally intact. This membrane fraction represents about 20% of the total protein of the respective organelle. Analysis of the flagellar membrane by sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis revealed one principal protein component, periodic acid-Schiff (PAS) positive and migrating with an apparent molecular weight of 250,000. The remaining minor proteins, none of them PAS positive, accounted for less than one-third of the total flagellar membrane fraction. Analysis of the ciliary membrane also revealed one major protein component, weakly PAS positive and migrating with an apparent molecular weight of 55,000. The remaining minor proteins represented about one-third of the total ciliary membrane fraction; two components with molecular weights of 100,000 and 40,000 predominated. The latter could be substantially reduced by purification of the cilia on a sucrose density gradient and was assumed to be actin, derived by vesiculation of the brush border during deciliation. The principal ciliary membrane protein, that of 55,000 daltons, was resolved into two equimolar components on NaDodSO4-Tris-glycine-polyacrylamide gels, comigrating with the alpha and beta chains of outer fiber tubulin. S-carboxymethylation caused increased splitting of the two components and concomitant migration with similarly treated ciliary tubulin. Preparative gel electrophoresis yielded separate components whose cyanogen bromide cleavage products were virtually identical in size distribution with those obtained from outer fiber alpha and beta chains; tryptic peptides corresponded almost exactly to those of authentic tubulin subunits but certain positional differences indicated possible side chain modification. At 25 degrees C both whole cilia and its solubilized membrane fraction bound colchicine while whole flagella and the 9 + 2 axoneme from either organelle did not. Thus certain molluscan flagellar membranes primarily contain a 250,000-dalton glycoprotein but ciliary membranes have a modified tubulin as the major protein component. At an electron microscopic level, flagellar membranes have a distinct trilamellar "unit membrane" structure while ciliary membranes appear thinner and considerably less distinct, perhaps reflecting the protein compositional differences in the membranes of these other wise morpholobically identical organelles.

Animals↗
PubMedDate not supplied

Immunolocalization of centriole-associated striated rootlets in human submandibular gland cells with and without solitary cilia.

Using an antibody specific to striated rootlets, we investigated the immuolocalization of striated rootlets in cells constituting human submandibular glands. Striated rootlets were positively stained in all cell types constituting acini, intercalated ducts, striated ducts, and interlobular ducts, but their shapes were different. The mean lengths of striated rootlets were 1.46 +/- 0.49, 3.15 +/- 1.35 and 3.99 +/- 1.02 microm in acinar secretory cells, myoepithelial cells, and columnar cells of the striated duct, respectively. The rootlets were the longest in columnar cells of the striated duct, in which paired centrioles were located in the apical cytoplasm away from nuclei. These findings suggest that striated rootlets play important roles in the positioning of centrioles in the cell. 2-8% of striated rootlets in myoepithelial cells were associated with solitary cilia, but they were not associated with solitary cilia in acinar cells and columnar cells of the striated duct. These observations suggest that striated rootlets may be associated with centrioles under normal physiological conditions, without formation of solitary cilia.

Centrioles↗
PubMed2005

Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability to generate primary cilia.

Outer dense fibre 2 (Odf2; also known as cenexin) was initially identified as a main component of the sperm tail cytoskeleton, but was later shown to be a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles. Here we show that Odf2 expression is suppressed in mouse F9 cells when both alleles of Odf2 genes are deleted. Unexpectedly, the cell cycle of Odf2(-/-) cells does not seem to be affected. Immunofluorescence and ultrathin-section electron microscopy reveals that in Odf2(-/-) cells, distal/subdistal appendages disappear from mother centrioles, making it difficult to distinguish mother from daughter centrioles. In Odf2(-/-) cells, however, the formation of primary cilia is completely suppressed, although approximately 25% of wild-type F9 cells are ciliated under the steady-state cell cycle. The loss of primary cilia in Odf2(-/-) F9 cells can be rescued by exogenous Odf2 expression. These findings indicate that Odf2 is indispensable for the formation of distal/subdistal appendages and the generation of primary cilia, but not for other cell-cycle-related centriolar functions.

Animals↗
PubMed2005

Cilia and Hedgehog responsiveness in the mouse.

The intraflagellar transport (IFT) proteins Ift172/Wimple and Polaris/Ift88 and the anterograde IFT motor kinesin-II are required for the production and maintenance of cilia. These proteins are also required for the activation of targets of the mouse Hedgehog (Hh) pathway by Gli transcription factors. The phenotypes of the IFT mutants, however, are not identical to mutants that lack Smoothened (Smo), an essential activator of the Hh pathway. We show here that mouse embryos that lack both Ift172 and Smo are identical to Ift172 single mutants, which indicates that Ift172 acts downstream of Smo. Ift172 mutants have a weaker neural patterning phenotype than Smo mutants, because Ift172, but not Smo, is required for proteolytic processing of Gli3 to its repressor form. Dnchc2 and Kif3a, essential subunits of the retrograde and anterograde IFT motors, are also required for both formation of Gli activator and proteolytic processing of Gli3. As a result, IFT mutants display a loss of Hh signaling phenotype in the neural tube, where Gli activators play the major role in pattern formation, and a gain of Hh signaling phenotype in the limb, where Gli3 repressor plays the major role. Because both anterograde and retrograde IFT are essential for positive and negative responses to Hh, and because cilia are present on Hh responsive cells, it is likely that cilia act as organelles that are required for all activity of the mouse Hh pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2003

IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia.

Intraflagellar transport (IFT) is an evolutionarily conserved mechanism thought to be required for the assembly and maintenance of all eukaryotic cilia and flagella. Although IFT proteins are present in cells with sensory cilia, the organization of IFT protein complexes in those cells has not been analyzed. To determine whether the IFT complex is conserved in the sensory cilia of photo-receptors, we investigated protein interactions among four mammalian IFT proteins: IFT88/Polaris, IFT57/Hippi, IFT52/NGD5, and IFT20. We demonstrate that IFT proteins extracted from bovine photoreceptor outer segments, a modified sensory cilium, co-fractionate at approximately 17 S, similar to IFT proteins extracted from mouse testis. Using antibodies to IFT88 and IFT57, we demonstrate that all four IFT proteins co-immunoprecipitate from lysates of mouse testis, kidney, and retina. We also extended our analysis to interactions outside of the IFT complex and demonstrate an ATP-regulated co-immunoprecipitation of heterotrimeric kinesin II with the IFT complex. The internal architecture of the IFT complex was investigated using the yeast two-hybrid system. IFT20 exhibited a strong interaction with IFT57/Hippi and the kinesin II subunit, KIF3B. Our data indicate that all four mammalian IFT proteins are part of a highly conserved complex in multiple ciliated cell types. Furthermore, IFT20 appears to bridge kinesin II with the IFT complex.

Adenosine Triphosphate↗
PubMedDate not supplied

Computer-assisted analysis of radial symmetry in human airway epithelial cilia: assessment of congenital ciliary defects in primary ciliary dyskinesia.

The ultrastructural analysis of cilia and diagnosis of primary ciliary dyskinesia (PCD) in biopsies of airway epithelium is sometimes confounded by poor sampling, inconsistencies in tissue quality and processing, and other technical problems. Although clinical findings may lead to a presumptive diagnosis, ultrastructural analysis of ciliary axonemes is the standard for confirmation of PCD. The ultrastructural features of the cilium when viewed in cross section by transmission electron microscopy confer a radial symmetry to the axoneme. Current digital image processing techniques can be applied to such images to reinforce signal, diminish noise, and confirm consistency of position of axonemal structures, a process that can augment ultrastructural analysis for PCD. In this study, computer-assisted digital image processing was used to evaluate cross sections of cilia in airway epithelial biopsies from patients previously diagnosed with PCD as well as in control subjects with normal cilia. These studies supported the original diagnoses and provided some new insights into axonemal organization in PCD. This technique is simple and may be useful in providing a supporting means for confirming or ruling out a diagnosis of PCD in cases that appear equivocal.

Chronic Disease↗
PubMed1961

The relationship between the fine structure and direction of beat in gill cilia of a lamellibranch mollusc.

This paper describes the fine structure and its relationship to the direction of beat in four types of cilia on the gill of the fresh-water mussel Anodonta cataracta. The cilia contain nine outer, nine secondary, and two central fibers, such as have been described previously in other material. Each outer fiber is a doublet with one subfiber bearing arms. One particular pair of outer fibers (numbers 5 and 6) are joined together by a bridge. The two central fibers are enclosed by a central sheath; also present in this region is a single, small mid-fiber. The different groups of fibers are connected together by radial links that extend from the outer to the secondary fibers, and from the secondary fibers to the central sheath. The basal body consists of a cylinder of nine triplet fibers. Projecting from it on one side is a dense conical structure called the basal foot. The cylinder of outer fibers continues from the basal body into the cilium, passing through a complex transitional region in which five distinct changes of structure occur at different levels. There are two sets of fibers associated with the basal bodies: a pair of striated rootlets that extends from each basal body down into the cell, and a system of fine tubular fibers that runs parallel to the cell surface. The relationship between fine structure and direction of beat is the same in all four types of cilia examined. The plane of beat is perpendicular to the plane of the central fibers, with the effective stroke toward the bridge between outer fibers 5 and 6, and toward the foot on the basal body.

Animals↗
PubMed2000

Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella.

Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit of the IFT particle and identified a Chlamydomonas insertional mutant that is missing this gene. The phenotype of this mutant is normal except for the complete absence of flagella. IFT88 is homologous to mouse and human genes called Tg737. Mice with defects in Tg737 die shortly after birth from polycystic kidney disease. We show that the primary cilia in the kidney of Tg737 mutant mice are shorter than normal. This indicates that IFT is important for primary cilia assembly in mammals. It is likely that primary cilia have an important function in the kidney and that defects in their assembly can lead to polycystic kidney disease.

Amino Acid Sequence↗
PubMed1966

Ultrastructural organization of cilia and basal bodies of the epithelium of the choroid plexus in the chick embryo.

Ultrastructural studies were performed on normal and abnormal cilia and basal bodies associated with the choroidal epithelium of the chick embryo. Tissues were prepared in each of several fixatives including: 1% osmium tetroxide, in both phosphate and veronal acetate buffers; 2% glutaraldehyde, followed by postfixation in osmium tetroxide; 1% potassium permanganate in veronal acetate buffer. Normal cilia display the typical pattern of 9 peripheral doublets and 2 central fibers, as well as a system of 9 secondary fibers. The latter show distinct interconnections between peripheral and central fibers. Supernumerary fibers were found to occur in certain abnormal cilia. The basal body is complex, bearing 9 transitional fibers at the distal end and numerous cross-striated rootlets at the proximal end. The distal end of the basal body is delimited by a basal plate of moderate density. The tubular cylinder consists of 9 triple fibers. The C subfibers end at the basal plate, whereas subfibers A and B continue into the shaft of the cilium. The 9 transitional fibers radiate out from the distal end of the basal body, ending in bulblike terminal enlargements which are closely associated with the cell membrane in the area of the basal cup. One or 2 prominent basal feet project laterally from the basal body. These structures characteristically show several dense cross-bands and, on occasion, are found associated with microtubules.

Animals↗
PubMed1968

Studies on cilia. 3. Further studies on the cilium tip and a "sliding filament" model of ciliary motility.

This study confirms and extends previous work on the lateral cilia of the fresh-water mussel, Elliptio complanatus, in support of a "sliding filament" mechanism of ciliary motility wherein peripheral filaments (microtubules) do not change length during beat (see Satir, 1967). Short sequences of serial sections of tips are examined in control (nonbeating) and activated (metachronal wave) preparations. Several different tip types, functional rather than morphogenetic variants, are demonstrated, but similarly bent cilia have similar tips. The peripheral filaments are composed of two subfibers: a and b. The bent regions of cilia are in the form of circular arcs, and apparent differences in subfiber-b length at the tip are those predicted solely by geometry of the stroke without the necessity of assuming filament contraction. Various subfibers b apparently move with respect to one another during beat, since small systematic variations in relative position can be detected from cilium to cilium. While subfiber-b lengths are uniform throughout, subfiber-a lengths are morphologically different for each filament: 8 and 3 are about 0.8 micro longer than 1, 4 and 5, but each unique length is independent of stroke position or tip type. Subfiber-a does not contract, nor does it move, e.g. slide, with respect to subfiber-b of the same doublet. The central pair of filaments extends to the tip of the cilium where its members fuse. Subunit assembly in ciliary microtubules is evidently precise. This may be of importance in establishing the relationships needed for mechanochemical interactions that produce sliding and beat.

Cilia↗
PubMed1980

Biochemical studies of the excitable membrane of Paramecium tetraurelia. III. Proteins of cilia and ciliary membranes.

As a first step in the biochemical analysis of membrane excitation in wild-type Paramecium and its behavioral mutants we have defined the protein composition of the ciliary membrane of wild-type cells. The techniques for the isolation of cilia and ciliary membrane vesicles were refined. Membranes of high purity and integrity were obtained without the use of detergents. The fractions were characterized by electron microscopy, and the proteins of whole cilia, axonemes, and ciliary membrane vesicles were resolved by SDS polyacrylamide gel electrophoresis and isoelectric focusing in one and two dimensions. Protein patterns and EM appearance of the fractions were highly reproducible. Over 200 polypeptides were present in isolated cilia, most of which were recovered in the axonemal fraction. Trichocysts, which were sometimes present as a minor contaminant in ciliary preparations, were composed of a very distinct set of over 30 polypeptides of mol wt 11,000--19,000. Membrane vesicles contained up to 70 polypeptides of mol wt 15,000--250,000. The major vesicle species were a high molecular weight protein (the "immobilization antigen") and a group of acidic proteins with mol wt similar to or approximately 40,000. These and several other membrane proteins were specifically decreased or totally absent in the axoneme fraction. Tubulin, the major axonemal species, occurred only in trace amounts in isolated vesicles; the same was true for Tetrahymena ciliary membranes prepared by the methods described in this paper. A protein of mol wt 31,000, pI 6.8, was virtually absent in vesicles prepared from cells in exponential growth phase, but became prominent early in stationary phase in good correlation with cellular mating reactivity. This detailed characterization will provide the basis for comparison of the ciliary proteins of wild-type and behavioral mutants and for analysis of topography and function of membrane proteins. It will also be useful in future studies of trichocysts and mating reactions.

Animals↗
PubMed1982

Specific localization of scallop gill epithelial calmodulin in cilia.

Calmodulin has been isolated and characterized from the gill of the bay scallop aequipecten irradians. Quantitative electrophoretic analysis of epithelial cell fractions show most of the calmodulin to be localized in the cilia, specifically in the detergent- solubilized membrane-matrix fraction. Calmodulin represents 2.2 +/- 0.3 percent of the membrane-matrix protein or 0.41 +/- 0.5 percent of the total ciliary protein. Its concentration is at least 10(-4) M if distributed uniformly within the matrix. Extraction in the presence of calcium suggests that the calmodulin is not bound to the axoneme proper. The ciliary protein is identified as a calmodulin on the basis of its calcium- dependent binding to a fluphenazine-sepharose affinity column and its comigration with bovine brain calmodulin on alkaline-urea and SDS polyacrylamide gels in both the presence and absence of calcium. Scallop ciliary calmodulin activates bovine brain phosphodiesterase to the same extent as bovine brain and chicken gizzard calmodulins. Containing trimethyllysine and lacking cysteine and tryptophan, the amino acid composition of gill calmodulin is typical of known calmodulins, except that it is relatively high in serine and low in methionine. Its composition is less acidic than other calmodulins, in agreement with an observed isoelectric point approximately 0.2 units higher than that of bovine brain. Comparative tryptic peptide mapping of scallop gill ciliary and bovine brain calmodulins indicates coincidence of over 75 percent of the major peptides, but at least two major peptides in each show no near-equivalency. Preliminary results using ATP-reactivated gill cell models show no effect of calcium at micromolar levels on ciliary beat or directionality of the lateral cilia, the cilia which constitute the vast majority of those isolated. However, ciliary arrest will occur at calcium levels more than 150 muM. Because calmodulin usually functions in the micromolar range, its role in this system is unclear. Scallop gill ciliary calmodulin may be involved in the direct regulation of dyneintubule sliding, or it may serve some coupled calcium transport function. At the concentration in which it is found, it must also at least act as a calcium buffer.

Amino Acids↗
PubMed1952

Effect of influenza virus on cilia and epithelial cells in the bronchi of mice.

In order to determine the effect of infection with influenza virus on bronchial cilia of the mouse, ciliary beat has been visualized directly by microscopic examination of the bronchi in slices of fresh lung. Cilia have been shown also in sections of fixed tissue by the use of special silver staining methods. The results have shown persistence of the cilia in spite of severe viral infection and indicate that the lowered resistance to secondary pneumococcal infection which occurs in influenzal pneumonia of the mouse is not due to interference with the ciliary mechanism. By a process of exclusion, the findings give further support to the theory that lowered resistance to pneumococcal infection in influenzal pneumonia is due to edema fluid in the viral lesion furnishing a culture medium for inhaled pneumococci. A widely used method for evaluation of ciliary activity on respiratory epithelia has been the microscopic observation of wave-like movements in reflected light. This activity was observed readily in the bronchi of mice but evidence was obtained showing that at this site it was due to something other than ciliary beat. Further histopathologic observations were made in order to define the lesion of the bronchial epithelium that would permit sparing of ciliated cells. In addition to usual techniques, mice were injected with colchicine for estimation of the rate of cellular proliferation and were exposed to a large dose of roentgen rays to eliminate polymorphonuclear leucocytes. Stains for mucous and for mitochondria were done also. The evidence obtained favors the theory that the viral infection does not destroy any of the cells of the bronchial epithelium. Inclusion bodies were found in the cytoplasm, making it seem likely instead that viral particles grow in colony-like aggregations and that liberation of virus into the lumen takes place not only by simple extrusion of inclusions but also by detachment of inclusion-laden globular portions of the cytoplasm.

Animals↗
PubMed2006

Soluble mediators, not cilia, determine airway surface liquid volume in normal and cystic fibrosis superficial airway epithelia.

A key aspect of the lung's innate defense system is the ability of the superficial epithelium to regulate airway surface liquid (ASL) volume to maintain a 7-mum periciliary liquid layer (PCL), which is required for cilia to beat and produce mucus flow. The mechanisms whereby airway epithelia regulate ASL height to >or=7 microm are poorly understood. Using bumetanide as an inhibitor of Cl- secretion, and nystatin as an activator of Na+ absorption, we found that a coordinated "blending" of both Cl- secretion and Na+ absorption must occur to effect ASL volume homeostasis. We then investigated how ASL volume status is regulated by the underlying epithelia. Cilia were not critical to this process as (a) ASL volume was normal in cultures from patients with primary ciliary dyskinesia with immotile cilia, and (b) in normal cultures that had not yet undergone ciliogenesis. However, we found that maneuvers that mimic deposition of excess ASL onto the proximal airways, which occurs during mucociliary clearance and after glandular secretion, acutely stimulated Na+ absorption, suggesting that volume regulation was sensitive to changes in concentrations of soluble mediators in the ASL rather than alterations in ciliary beating. To investigate this hypothesis further, we added potential "soluble mediators" to the ASL. ASL volume regulation was sensitive to a channel-activating protein (CAP; trypsin) and a CAP inhibitor (aprotinin), which regulated Na+ absorption via changes in epithelial Na+ channel (ENaC) activity in both normal and cystic fibrosis cultures. ATP was also found to acutely regulate ASL volume by inducing secretion in normal and cystic fibrosis (CF) cultures, while its metabolite adenosine (ADO) evoked secretion in normal cultures but stimulated absorption in CF cultures. Interestingly, the amount of ASL/Cl- secretion elicited by ATP/ADO was influenced by the level of CAP-induced Na+ absorption, suggesting that there are important interactions between the soluble regulators which finely tune ASL volume.

Adenosine↗
PubMed1963

ELECTRICAL RESPONSE AND GROWTH OF OLFACTORY CILIA OF THE OLFACTORY EPITHELIUM OF THE NEWT IN WATER AND ON LAND.

A correlation between the length of the olfactory cilia and the electrical activity of the olfactory epithelium was studied in newts living in water and on land. The olfactory cilia grew when newts were transferred onto land. The cilia in the olfactory bud became longest in 108 hours after the transfer and then became shorter, while those in the interstitium only gradually elongated. Slow potentials were evoked in the epithelium by the application of odorous fluids but not by odorous vapors for 20 hours after the transfer. Thereafter, the slow potential began to appear in response to odorous vapors and reached maximal magnitude between 60 and 70 hours after the transfer, while it was not evoked by odorous fluids in this period. In the later stage, the slow potential to odorous vapors decreased in magnitude and disappeared 120 hours after the transfer, while it began to reappear in response to odorous fluids. When these changes in the slow potential were compared with those in the cilium, a discrepancy was found between the period of maximal potential magnitude and that of maximal cilium length.

Animals↗
PubMed2004

A NIMA-related kinase, Fa2p, localizes to a novel site in the proximal cilia of Chlamydomonas and mouse kidney cells.

Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.

Animals↗
PubMed2002

Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle.

Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin interacts with the anaphase promoting complex protein Apc2. As expected of an Apc2 target, inversin possesses D-boxes and site-directed mutagenesis of the well-conserved D-box residues abrogates inversin-Apc2 interaction. An inversin-specific antibody reveals a dynamic expression pattern throughout the cell cycle and strong expression in the primary cilia of renal epithelium. Our data support a role for inversin in primary cilia and involvement in the cell cycle. Mutations of the proteins polaris, cystin and polycystin-2 which are expressed in renal epithelium primary cilia, lead to renal cystic changes. Aberrant cell proliferation is also involved in cyst development. The data reported here suggest that inversin may provide a link between these two mechanisms.

Amino Acid Motifs↗