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PubMed1994

Cytosolic guanine nucleotide-binding protein Rac2 operates in vivo as a component of the neutrophil respiratory burst oxidase. Transfer of Rac2 and the cytosolic oxidase components p47phox and p67phox to the submembranous actin cytoskeleton during oxidase activation.

The respiratory burst oxidase is responsible for O2- production in stimulated neutrophils and B lymphocytes. Components of this oxidase include cytochrome b558, a membrane-bound flavohemoprotein; the cytosolic polypeptides p47phox and p67phox; and one or more small G proteins including Rac1, Rac2, and/or Rap1A. We found that when normal neutrophils were activated, small percentages of each of the cytosolic proteins p47phox, p67phox, and Rac2 were transferred to the membrane cytoskeleton. However, Rac2 was not transferred to the membrane during activation of p47phox-deficient neutrophils. In normal cells, some p47phox also became associated with the non-cytoskeletal portion of the plasma membrane, but p67phox, Rac2, and O(2-)-forming activity were restricted to the cytoskeleton. Neutrophil activation also causes the phosphorylation of multiple serines in p47phox. The most heavily phosphorylated forms of p47phox were found solely in the membrane cytoskeleton. These results suggest that 1) the membrane cytoskeleton participates in respiratory burst oxidase activation, 2) the fully phosphorylated p47phox is located in the active oxidase, which resides in the membrane cytoskeleton, and 3) Rac2 acts like a dedicated component of the respiratory burst oxidase.

Actins↗
PubMed1993

Thermal injury-induced changes in the rat intestine brush border cytoskeleton.

BACKGROUND: The brush border cytoskeleton maintains the selective absorptive surface of the intestine epithelium. Increased intestinal permeability caused by cutaneous thermal injury may be the result of changes in the organization of the brush border cytoskeleton. METHODS: In this study we used electron and laser confocal microscopy to examine the temporal and spatial organization of the rat brush border cytoskeleton after thermal injury. RESULTS: Vesiculation of microvilli and disruption of core actin filament bundles were observed in rats with burns covering 20% total body surface area (TBSA). In rats with 40% TBSA burns changes in the brush border cytoskeleton were more pronounced, resulting in increased vesiculation of microvilli and disruption of terminal web actin filaments. Confocal microscopy of corresponding areas of the gut epithelium after staining with rhodamine-phalloidin showed rearrangement of brush border actin filaments. Although tight junctions were intact, the apical region of the gut epithelium in rats with 40% TBSA burns was constricted, possibly because of contraction of brush border actin filaments. Changes in brush border structure and cytoskeletal organization were most pronounced in the ileum of rats 18 hours after injury. CONCLUSIONS: These findings suggest that disruption of the brush border cytoskeleton may, in part, be responsible for the loss of intestinal barrier function after thermal injury in animal models.

Actins↗
PubMed1996

Fertilization promotes selective association of the Abl [correction of AbI] kinase with the egg cytoskeleton.

Fertilization of the sea urchin egg is known to involve activation of a variety of protein kinases including at least one protein tyrosine kinase. In the present study, fertilization was found to stimulate the association of the Abl [correction of AbI] protein kinase with the detergent-insoluble egg cytoskeleton. Increased levels of Abl protein and of protein tyrosine kinase activity were detected in cytoskeleton preparations made as early as 5 to 15 min after insemination. Immunofluorescence localization demonstrated that the Abl kinase becomes associated primarily with the cortical cytoskeleton of the fertilized egg. A separate, 57 kDa protein tyrosine kinase did not associate with the cytoskeleton indicating that fertilization results in the selective association of the Abl kinase with the cortical cytoskeleton.

Animals↗
PubMed1996

Hemodynamic forces modulate simultaneously the release of growth factors and the organisation of cytoskeleton of aortic smooth muscle-cells.

Recurrent stenosis because of myointimal hyperplasia or atherosclerosis after carotid endarterectomy occurs in 5-15% of the cases. The key event is the abnormal proliferation of arterial Smooth Muscle Cells (SMC). After endarterectomy SMC are directly exposed to the blood flowing under pressure. The aim of the present study was to determine the changes in morphology, cytoskeleton organisation, and release of growth factors by SMC exposed to laminar flow. Subconfluent SMC were exposed to a level of shear stress of 6 dyne/cm2 (100 ml/min) for 24 hours under conditions of steady laminar flow. The changes in morphology and cytoskeleton organisation were analysed by light and scanning electron microscopy, and by fluorescence microscopy. Growth factors release was assessed by ELISA. After exposure to laminar flow, SMC assumed a spindle-like shape; they lost many of their protrusions and there was a clear reorganisation of the cytoskeleton and simultaneously their released a higher quantity of PDGF and bFGF. In this study, we found simultaneous changes in cytoskeleton organisation and release of growth factors in SMC exposed to flow. Cytoskeleton reorganisation might be the mechanism through which SMC respond to changes in blood flow. These findings may help to explain the genesis of myointimal hyperplasia following carotid endarterectomy.

Cytoskeleton↗
PubMed1979

Integral membrane protein interaction with Triton cytoskeletons of erythrocytes.

The organization of erythrocyte membrane lipids and proteins has been studied following the release of cytoplasmic components with the non-ionic detergent Triton X-100. After detergent extraction, a detergent-resistant complex called the erythrocyte cytoskeleton is separated from detergent, solubilized lipid and protein by sucrose buoyant density sedimentation. In cytoskeletons prepared under isotonic conditions all of the major erythrocyte membrane proteins are retained except for the integral protein, glycophorin, which is quantitatively solubilized and another integral glycoprotein, band 3, which is only 60% removed. When cytoskeletons are prepared in hypertonic KCl solutions, band 3 is fully solubilized along with bands 2.1 and 4.2 and several minor components. The resulting cytoskeletons have the same morphology as those prepared in isotonic buffer but they are composed of only three major peripheral proteins, spectrin, actin and band 4.1. We have designated this peripheral protein complex the 'shell' of the erythrocyte membrane, and have shown that the attachment of band 3 to the shell satisfies the criteria for a specific interaction. Although Triton did affect erythrocyte shape, cytoskeleton lipid content and the activity of membrane proteases, there was no indication that Triton altered the attachment of band 3 to the shell. We suggest that band 3 attaches to the shell as part of a ternary complex of bands 2.1, 3 and 4.2.

Erythrocyte Membrane↗
PubMed1981

In vitro phosphorylation of the red blood cell cytoskeleton complex by cyclic AMP-dependent protein kinase from erythrocyte membrane.

Hydrosoluble proteins extracted from human erythrocyte ghosts by dialysis at low ionic strength and alkaline pH contain a cyclic AMP-dependent protein kinase which phosphorylates in vitro the cytoskeleton components in crude extracts. Spectrin components 1 and 2, actin and protein band 4.1 undergo this cyclic AMP-dependent endogenous phosphorylation together with low molecular weight peptides solubilized with the cytoskeleton in hydrosoluble extract. However, pure spectrin and purified erythrocyte G-actin were not phosphorylated by purified cyclic AMP-dependent protein kinase from erythrocyte membrane. Purified G-actin when added free to crude extract does not undergo phosphorylation by the cyclic AMP-dependent protein kinase present in this extract. In contrast, purified cyclic AMP-dependent protein kinase added either to crude extract or to the purified cytoskeleton complex (spectrin, actin and protein band 4.1), phosphorylates spectrin, actin and protein band 4.1. We can conclude that (1) cyclic AMP-dependent phosphorylation of red cell cytoskeleton occurs in vitro only when the cytoskeleton components are in a complexed form; (2) red cell actin, like other cellular actins, may be phosphorylated by cyclic AMP-dependent protein kinase but only in the oligomeric form and not in the G form.

Actins↗
PubMed1988

Isolated cytoskeletons of human blood platelets: dark-field imaging of coiled and uncoiled microtubules.

Detergent extraction of human blood platelets pre-treated with Taxol to stabilize microtubules allows isolation of marginal band (MB) cytoskeletons. We studied MB cytoskeleton structure using dark-field light microscopy and negative stain electron microscopy (EM). Dark-field illumination clearly demonstrated the "hoop" shape of MB cytoskeletons in unfixed suspensions where the microtubule coils had a mean diameter of 2.87 microns (+/- 0.18 micron, SD). Microtubules were uncoiled by brief exposure to trypsin (2 ng/micrograms protein) or by NaCl (154-600 mM) but not by DNase I, which removed approximately 40% of total actin, but had no effect on dark-field images of microtubule coils. As microtubules uncoiled, a single fiber emerged from the hoop and gradually lengthened as the brightness of the hoop diminished; these fibers correspond to the single microtubules seen by EM. Polypeptides of coiled and uncoiled MB cytoskeletons were analyzed by SDS-PAGE. When microtubules became uncoiled, no changes in the major components (alpha- and beta-tubulin, IEF-51K, or actin) were found. However, a number (greater than 10) of minor polypeptides, each less than 5% of total cytoskeletal protein and with an Mr ranging from 80,000- greater than 260,000, were decreased in "uncoiled" MB cytoskeletons. These results implicate one or more of these minor polypeptides in maintenance of hoop integrity. Dark-field light microscopy thus provides an approach toward investigating the mechanism(s) involved in maintaining the microtubule coil of the platelet marginal band.

Alkaloids↗
PubMed2001

A novel interaction of the Golgi complex with the vimentin intermediate filament cytoskeleton.

The integration of the vimentin intermediate filament (IF) cytoskeleton and cellular organelles in vivo is an incompletely understood process, and the identities of proteins participating in such events are largely unknown. Here, we show that the Golgi complex interacts with the vimentin IF cytoskeleton, and that the Golgi protein formiminotransferase cyclodeaminase (FTCD) participates in this interaction. We show that the peripherally associated Golgi protein FTCD binds directly to vimentin subunits and to polymerized vimentin filaments in vivo and in vitro. Expression of FTCD in cultured cells results in the formation of extensive FTCD-containing fibers originating from the Golgi region, and is paralleled by a dramatic rearrangements of the vimentin IF cytoskeleton in a coordinate process in which vimentin filaments and FTCD integrate into chimeric fibers. Formation of the FTCD fibers is obligatorily coupled to vimentin assembly and does not occur in vim(-/-) cells. The FTCD-mediated regulation of vimentin IF is not a secondary effect of changes in the microtubule or the actin cytoskeletons, since those cytoskeletal systems appear unaffected by FTCD expression. The assembly of the FTCD/vimentin fibers causes a coordinate change in the structure of the Golgi complex and results in Golgi fragmentation into individual elements that are tethered to the FTCD/vimentin fibers. The observed interaction of Golgi elements with vimentin filaments and the ability of FTCD to specifically interacts with both Golgi membrane and vimentin filaments and promote their association suggest that FTCD might be a candidate protein integrating the Golgi compartment with the IF cytoskeleton.

Actins↗
PubMed1992

Association of Phosphatidylinositol 4-Kinase with the Plant Cytoskeleton.

In eukaryotic cells, phosphatidylinositol 4-hydroxy kinase and phosphatidylinositol-4-phosphate 5-hydroxy kinase are responsible for the formation of the two second messenger precursors phosphatidylinositol-4-phosphate (Ptdlns(4)P) and phosphatidylinositol-4,5-bisphosphate (Ptdlns(4,5)P2). In plant cells, these kinases have been considered to be exclusively membrane associated, with the majority of activity residing in the inner leaflet of the plasmalemma. By sequentially extracting carrot protoplasts with the detergent Nonidet P-40 then more rigorously with Triton X-100, we were able to remove the activity of three separate plasma membrane marker enzymes and to demonstrate that a significant proportion of cellular Ptdlns 4-kinase is associated with the cytoskeleton. When only endogenous substrates were present, Nonidet P-40-permeabilized protoplasts and Nonidet P-40-extracted cytoskeletons displayed a pattern of lipid phosphorylation similar to that obtained with isolated plant membranes or permeabilized cells, whereas the Triton X-100-extracted cytoskeletons showed little or no activity. In contrast, when exogenous substrates were added, a major proportion of PtdlnsP formed was due to kinase activity associated with the cytoskeleton as well as nuclei. However, by subtracting the activity of isolated nuclei, it could be demonstrated that a significant proportion of the detergent-resistant Ptdlns kinase activity resides with the cytoskeletal fraction. These findings suggest that the pathways of polyphosphoinositide biosynthesis in plant cells should be reevaluated to take account of the cytoskeleton and that Ptdlns(4)P itself may play a unique role in modulation of plant cytoskeletal integrity and cellular signal transduction.

Journal Article↗
PubMedDate not supplied

Osmotic stress and the cytoskeleton: the R(h)ole of Rho GTPases.

Hyperosmotic stress initiates a variety of compensatory and adaptive responses, which either serve to restore near-normal volume or remodel and reinforce the cell structure to withstand the physical challenge. The latter response is brought about by the reorganization of the cytoskeleton; however, the underlying mechanisms are not well understood. Recent research has provided major breakthroughs in our knowledge about the link between message and structure, i.e. between signalling and cytoskeletal remodelling, predominantly in the context of cell migration. The major components of this progress are the in-depth characterization of Rho family small GTPases, master regulators of the cytoskeleton, and the discovery of the actin-related protein 2/3 complex, a signalling-sensitive structural element of the actin polymerization machinery. The primary aim of this review is to find the place of these novel and crucial players in osmotically induced (volume-dependent) remodelling of the cytoskeleton. We aim to address three questions: (1) What are the major structural changes in the cytoskeleton under hyperosmotic conditions? (2) Are the Rho family small GTPases (Rho, Rac and Cdc42) regulated by osmotic stress, and if so, by what mechanisms? (3) Are Rho GTPases involved, as mediators, in major adaptive responses, including cytoskeleton rearrangement, changes in ion transport and genetic reprogramming? Our answers will show how fragmentary our current knowledge is in these areas. Therefore, this overview has been written with the hardly disguised intention that it might foster further research in this field by highlighting some intriguing questions.

Actins↗
PubMed1981

Isolation of the cytoskeleton from Giardia. Tubulin and a low-molecular-weight protein associated with microribbon structures.

The sucking disk of Giardia is supported by a large, plate-like organelle: the ventral disk cytoskeleton. Extraction by Triton-X 100 of Giardia trophozoites from the mouse gut, or of G. duodenalis or G. lamblia grown from cultures, yields cell-free disk cytoskeletons. Up to 8 flagellar axonemes may be attached to an isolated disk. Disks are seen in the electron microscope to be composed of concentrically coiled microtubules bonded to microribbons. Microribbons are large, laminated structures, linked by dense networks of crossbridges. They are made up of regularly arranged subunits. Microtubules and microribbons are preserved in Triton for long periods, but crossbridges are slowly dissolved. Whereas the addition of ATP causes axonemes to resume bending, active movements were not detected in disks. It seems more likely that a disk is a passive effector, which may be acted upon by other contractile structures of the cytoplasm. It is highly specialized and quintessential cytoskeleton. Disks and axonemes will dissolve in sodium dodecyl sulphate (SDS), and after SDS-gel electrophoresis 2 prominent bands are apparent. One, corresponding to tubulin, migrates in low ionic strength, high pH buffers as 2 closely spaced bands of equal staining density. The other, a smaller protein, is a complex polypeptide band of molecular weight 30 000 Daltons. Allowing for staining differences, the 2 proteins are probably present in cytoskeletons in roughly equal amounts. Because of their size microribbons account for at least 75% of the structured material stained by electron stains in pellets of cytoskeletons. Disk and axoneme microtubules comprise the minority fraction. This result suggests that, like microtubules, microribbons are a source of structural tubulin and probably also contain the 30 000 mol. wt protein.

Animals↗
PubMed1981

Possible roles for the membrane cytoskeleton in regulating red cell stability and deformability.

Several observations suggest the presence of a membrane cytoskeleton in the red cell. Some of these imply possible roles for that cytoskeleton in regulating red cell shape and deformability. One of the most striking examples of this role is that of the spectrin-free spherocyte mouse. In this condition, spectrin is virtually absent from the membranes of erythrocyte cells and osmotic fragility and survival is markedly affected. The mice are afflicted with an extreme haemolytic anaemia which is barely compatible with life. An unequivocal role for the cytoskeleton in being responsible for this disorder has been shown through experiments in which the cytoskeleton has been reconstituted by specific rebinding of normal mouse spectrin to these defective cell membranes. Marked improvement in membrane fragmentation, membrane, membrane fusion, and osmotic stability following reconstitution indicated that these functions are partially regulated through the membrane cytoskeleton, and its predominant protein, spectrin.

Anemia, Hemolytic↗
PubMed1994

Role of the microtubule cytoskeleton in gravisensing Chara rhizoids.

The arrangement of the microtubule cytoskeleton in tip-growing and gravisensing Chara rhizoids has been documented by immunofluorescence microscopy. Predominantly axially oriented undulating bundles of cortical microtubules were found in the basal zone of the rhizoids and colocalized with the microfilament bundles underlying the cytoplasmic streaming. Microtubules penetrate the subapical zone, forming a three-dimensional network that envelops the nucleus and organelles. Microtubules are present up to 5 to 10 microns basal from the apical cytoplasmic region containing the statoliths. No microtubules were found in the apical zone of the rhizoid which is the site of tip growth and gravitropism. Depolymerization of microtubules by application of oryzalin does not affect cytoplasmic streaming and gravitropic growth until the relatively stationary and polarly organized apical and subapical cytoplasm is converted into streaming cytoplasm. When the statoliths and the apical cytoplasm are included in the cytoplasmic streaming, tip growth and gravitropism are stopped. Oryzalin-induced disruption of the microtubule cytoskeleton also results in a rearrangement of the dense network of apical and subapical microfilaments into thicker bundles, whereas disruption of the microfilament cytoskeleton by cytochalasin D had no effect on the organization of the microtubule cytoskeleton. It is, therefore, concluded that the arrangement of microtubules is essential for the polar cytoplasmic zonation and the functionally polar organization of the actin cytoskeleton which is responsible for the motile processes in rhizoids. Microtubules are not involved in the primary events of gravitropism in Chara rhizoids.

Chlorophyta↗
PubMed1996

Comparative scanning, transmission and atomic force microscopy of the microtubular cytoskeleton in fenestrated liver endothelial cells.

Endothelial fenestrae control the exchange of fluids, solutes and particles between the sinusoidal lumen and the microvillous surface of the parenchymal cells. Fenestrae have a critical dimension in the order of 150-200 nm, making it necessary to use microscopes with a resolution better than the light microscope. Comparative whole-mount preparations of isolated, purified and cultured rat liver sinusoidal endothelial cells (LEC) were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Examination of detergent-extracted LEC by SEM and TEM shows an integral cytoskeleton: sieve plates are delineated by a sieve plate-associated cytoskeleton ring and fenestrae by a fenestrae-associated cytoskeleton ring. By using microtubule altering agents we could demonstrate: (1) the architectural role of microtubules in arranging fenestrae, (2) the existence of a population of microtubules resistant against low temperature and colchicine, (3) the ability of LEC to shift the microtubule assembly-disassembly steady state under various conditions, (4) and the necessity of an intact microtubular cytoskeleton to support the increase in the number of fenestrae after cytochalasin B. Topographical examinations of AFM images revealed that sieve plates are delineated by elevated borders, probably projections of the underlying tubular cytoskeleton.

Animals↗
PubMedDate not supplied

Cytoskeleton modifications induced by phenobarbital, 2-acetylaminofluorene and 4-acetylaminofluorene in normal and initiated/selected hepatocytes: relation with the "resistant" phenotype.

Initiated/selected (ISH) and normal (NH) rat hepatocytes were used to study cytoskeleton modifications induced by three liver acting chemicals: 2-AAF, a liver complete carcinogen; PB, a liver tumor promoter; and 4-AAF, a non-carcinogen analogue of 2-AAF. Cytoskeleton alterations were visualized by disappearance of F-actin fibers and tubulin depolymerization. The three drugs induced actin fragmentation in normal hepatocytes; a net loss of actin protein was observed with PB. They also induced varied tubulin depolymerization. The principal difference between chemicals is that 2-AAF led to non-reversible effects, in comparison with PB and 4-AAF which induced reversible damages on cytoskeleton. By contrast to normal hepatocytes, the cytoskeleton of ISH obtained from rats subjected to the "resistant" hepatocyte protocol was much less susceptible to the effect of the three chemicals. Moreover, we observed a lack of LDH release in the culture medium and a very rapid inducibility of GST activity after exposure of ISH to drugs. The moderate effect of the three chemicals on actin and tubulin in ISH could thus be explained by the "resistant" metabolic profile of these cells.

2-Acetylaminofluorene↗
PubMed2005

Morphological and oxidative alterations on Sertoli cells cytoskeleton due to retinol-induced reactive oxygen species.

Retinol (vitamin A) is involved in several cellular processes, like cell division, differentiation, transformation and apoptosis. Although it has been shown that retinol is a limitant factor for all these processes, the precise mechanisms by which retinol acts are still unknown. In the present study we hypothesised that alterations in the cytoskeleton of Sertoli cells induced by retinol supplementation could indicate an adaptive maintenance of its functions, since it plays an important role in the transformation process that we observed. Previous results demonstrated that Sertoli cells treated with retinol showed an oxidative imbalance, that leads the cell to two phenotypes: apoptosis or transformation. Our group has identified characteristics of Sertoli cells transformed by retinol which results in normal cell functions modification. In the present study the actin filament fluorescence assay and the deformation coefficient showed a modification in the morphology induced by retinol. We also observed an oxidative alteration in isolated cytoskeleton proteins and did not show alterations when these proteins are analyzed by electrophoreses. Our results showed an increase in mitochondria superoxide production and a decrease in nitric oxide levels. All results were partially or completely reverted by co-treatment of the antioxidant Trolox. These findings suggest that the cytoskeleton components suffer individual alterations in different levels and that these alterations generate a global phenotype modification and that these processes are probably ROS dependent. We believe that the results from this study indicate an adaptation of the cytoskeleton to oxidative imbalance since there was not a loss of its function.

Actin Cytoskeleton↗
PubMed1988

Cytoskeleton in preimplantation mouse development.

This paper reviews the constituents of the cytoskeleton in the cells of the preimplantation mouse embryo and how they change as the development proceeds. The cytoskeleton can be divided into two distinct groups, that in the cytosplasm and that associated with the membrane. The first and better-known group contains microfilaments, microtubules and intermediate filaments, the second such components of the cell and nuclear membrane as spectrin-like protein and nuclear lamin. The filamentous components of the cytoplasmic cytoskeleton adhere to the nuclear and cell membrane at attachment points where specific proteins such as vinculin may mediate the interaction. Each cell of the early embryo has all of these components, but their morphological organization and molecular constitution alter as the embryo develops. These modifications are especially pronounced when the cleavage-stage embryo compacts and when the blastocysts forms and differentiates. These events represent the most critical stages of morphogenesis and cytodifferentiation in the preimplantation embryo. The cytoskeleton may thus have an important role in the control of the early mammalian development.

Actin Cytoskeleton↗
PubMed1988

Association of African swine fever virus with the cytoskeleton.

The association of African swine fever virus (ASFV) with the cytoskeleton was investigated. Immunofluorescent studies of ASFV infected cells with anti-ASFV serum showed a temporal and spatial development of viral inclusions which moved from a peripheral to a perinuclear location and fused to give a single large perinuclear factory. The migration and fusion of viral inclusions was inhibited by colchicine suggesting a function for microtubules in assembly site organization not previously described. Accumulation of virions outside the inclusions and inhibition of viral release was also observed in colchicine treated cells. Viral antigens and structural elements were retained on the cytoskeleton fraction of Triton X-100 extracted cells. Reorganization of cytoskeletal elements around the assembly sites was demonstrated by transmission electronmicroscopy and by immunofluorescent studies using monoclonal antibodies against actin, tubulin and vimentin. Intermediate filaments accumulated around the viral factories, microtubules were greatly decreased in number and microfilaments were reorganized in association with the plasma membrane. Bundles of 15 nm tubules of unknown origin were also observed around the assembly sites. The distribution of viral proteins in soluble, cytoskeleton and detergent insoluble nuclear fractions was studied by pulse-chase experiments with [35S]methionine. SDS-PAGE analysis showed the presence in the cytoskeletal and nuclear fractions of 150, 72, 38, 28, 19 and 15 kDa virus structural proteins which increased after a 5 h chase. Our results indicate a close association of ASFV replication with the cytoskeleton similar to events described during FV3 replication but which differ from those occurring in poxvirus-infected cells.

Actin Cytoskeleton↗