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At least 235 records · Page 13Linked to original sources
PubMed2002

The PtdIns3P phosphatase myotubularin is a cytoplasmic protein that also localizes to Rac1-inducible plasma membrane ruffles.

Myotubularin, the phosphatase mutated in X-linked myotubular myopathy, was shown to dephosphorylate phosphatidylinositol 3-monophosphate (PtdIns3P) and was also reported to interact with nuclear transcriptional regulators from the trithorax family. We have characterized a panel of specific antibodies and investigated the subcellular localization of myotubularin. Myotubularin is not detected in the nucleus, and localizes mostly as a dense cytoplasmic network. Overexpression of myotubularin does not detectably affect vesicle trafficking in the mammalian cells investigated, in contrast to previous observations in yeast models. Both mutation of a key aspartate residue of myotubularin and dominant activation of Rac1 GTPase lead to the recruitment of myotubularin to specific plasma membrane domains. Localization to Rac1-induced ruffles is dependent on the presence of a domain highly conserved in the myotubularin family (that we named RID). We thus propose that myotubularin may dephosphorylate a subpool of PtdIns3P (or another related substrate) at the plasma membrane.

Animals↗
PubMed2006

Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement.

Cells lining the gastrointestinal tract serve as both a barrier to and a pathway for infectious agent entry. Dendritic cells (DCs) present in the lamina propria under the columnar villus epithelium of the small bowel extend processes across this epithelium and capture bacteria, but previous studies provided limited information on the nature of the stimuli, receptors, and signaling events involved in promoting this phenomenon. Here, we use immunohistochemical as well as dynamic explant and intravital two-photon imaging to investigate this issue. Analysis of CD11c-enhanced green fluorescent protein (EGFP) or major histocompatibility complex CII-EGFP mice revealed that the number of trans-epithelial DC extensions, many with an unusual "balloon" shape, varies along the length of the small bowel. High numbers of such extensions were found in the proximal jejunum, but only a few were present in the terminal ileum. The extensions in the terminal ileum markedly increased upon the introduction of invasive or noninvasive Salmonella organisms, and chimeric mouse studies revealed the key role of MyD88-dependent Toll-like receptor (TLR) signaling by nonhematopoietic (epithelial) elements in the DC extension response. Collectively, these findings support a model in which epithelial cell TLR signaling upon exposure to microbial stimuli induces active DC sampling of the gut lumen at sites distant from organized lymphoid tissues.

Animals↗
PubMed2002

Perikaryal surface specializations of neurons in sensory ganglia.

Slender projections, similar to microvilli, are the main specialization of the perikaryal surface of sensory ganglion neurons. The extent of these projections correlates closely with the volume of the corresponding nerve cell body. It is likely that the role of perikaryal projections of sensory ganglion neurons, which lack dendrites, is to maintain the surface-to-volume ratio of the nerve cell body above some critical level for adequate metabolic exchange. Satellite cells probably have the ability to promote, or provide a permissive environment for, the outgrowth of these projections. It is not yet known whether the effect of satellite cells is mediated by molecules associated with their plasma membrane or by diffusible factors. Furthermore, receptor molecules for numerous chemical agonists are located on the nerve cell body surface, but it is not known whether certain molecules are located exclusively on perikaryal projections or are also present on the smooth surface between these projections. Further study of the nerve cell body surface and of the influence that satellite cells exert on it will improve our understanding of the interactions between sensory ganglion neurons and satellite neuroglial cells.

Animals↗
PubMed2000

Peripodial cells regulate proliferation and patterning of Drosophila imaginal discs.

Cells employ a diverse array of signaling mechanisms to establish spatial patterns during development. Nowhere is this better understood than in Drosophila, where the limbs and eyes arise from discrete epithelial sacs called imaginal discs. Molecular-genetic analyses of pattern formation have generally treated discs as single epithelial sheets. Anatomically, however, discs comprise a columnar cell monolayer covered by a squamous epithelium known as the peripodial membrane. Here we demonstrate that during development, peripodial cells signal to disc columnar cells via microtubule-based apical extensions. Ablation and targeted gene misexpression experiments demonstrate that peripodial cell signaling contributes to growth control and pattern formation in the eye and wing primordia. These findings challenge the traditional view of discs as monolayers and provide foundational evidence for peripodial cell function in Drosophila appendage development.

Animals↗
PubMed2006

Cell distribution of stress fibres in response to the geometry of the adhesive environment.

Cells display a large variety of shapes when plated in classical culture conditions despite their belonging to a common cell type. These shapes are transitory, since cells permanently disassemble and reassemble their cytoskeleton while moving. Adhesive micropatterns are commonly used to confine cell shape within a given geometry. In addition the micropattern can be designed so as to impose cells to spread upon adhesive and nonadhesive areas. Modulation of the pattern geometry allows the analysis of the mechanisms governing the determination of cell shape in response to external adhesive conditions. In this study, we show that the acquisition of cell shape follows two stages where initially the cell forms contact with the micropattern. Here, the most distal contacts made by the cell with the micropattern define the apices of the cell shape. Then secondly, the cell borders that link two apices move so as to minimise the distance between the two apices. In these cell borders, the absence of an underlying adhesive substrate is overcome by stress fibres forming between the apices, which in turn are marked by an accumulation of focal adhesions. By inhibiting myosin function, cell borders on nonadhesive zones become more concave, suggesting that the stress fibres work against the membrane tension in the cell border. Moreover, this suggested that traction forces are unevenly distributed in stationary, nonmigrating, cells. By comparing the stress fibres in cells with one, two, or three nonadherent cell borders it was reasoned that stress fibre strength is inversely proportional to number. We conclude that cells of a given area can generate the same total sum of tractional forces but that these tractional forces are differently spaced depending on the spatial distribution of its adherence contacts.

Actins↗
PubMed2005

Local interactions shape plant cells.

Plant cell expansion is usually attributed to the considerable osmotic pressure that develops within and impinges upon the cell boundary. Whereas turgor containment within expandable walls explains global expansion, the scalar nature of turgor does not directly suggest a mechanism for achieving the localized, differential growth that is responsible for the diversity of plant-cell forms. The key to achieving local growth in plant cells appears to lie not in harnessing turgor but in using it to identify weak regions in the cell boundary and thus creating discrete intracellular domains for targeting the growth machinery. Membrane-interacting phospholipases, Rho-like proteins and their interactors, an actin-modulating ARP2/3 complex with its upstream regulators, and actin-microtubule interactions play important roles in the intracellular cooperation to shape plant cells.

Actin-Related Protein 2-3 Complex↗
PubMed2000

Intracellular survival by Chlamydia.

Chlamydiae are obligate intracellular bacterial pathogens whose entry into mucosal epithelial cells is required for intracellular survival and subsequent growth. After a seemingly stealthy entry, chlamydiae quickly modify their vacuole (i) for exit from the endosomal pathway to the exocytic pathway and (ii) to permit fusion with intercepted endoplasmic reticulum- and Golgi-derived vesicles carrying glycerophospholipids and sphingolipids for chlamydiae-containing vacuole membrane expansion. Chlamydiae possess novel hollow proteinaceous structures, termed projections, which they use to pierce the inclusion membrane, possibly to acquire from the epithelial cytoplasm nutrients they cannot synthesize; whether or not these truncated flagellar-like structures serve a dual exchange function for secretion of molecules to programme host cell signalling is unknown. Despite the accumulation of some 500-1000 progeny in the enormously enlarged inclusion, host cell function is surprisingly little disrupted, and progeny escape can be unobtrusive. This elegant adaptive pathogen strategy, which leads to silent, chronic human infection, is fascinating from a cellular microbiology perspective.

Cell Surface Extensions↗
PubMed2006

The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices.

Dipeptidyl peptidase IV (DPP4/CD26) and seprase/fibroblast activation protein alpha are homologous type II transmembrane, homodimeric glycoproteins that exhibit unique prolyl peptidase activities. Human DPP4 is ubiquitously expressed in epithelial and endothelial cells and serves multiple functions in cleaving the penultimate positioned prolyl bonds at the NH(2) terminus of a variety of physiologically important peptides in the circulation. Recent studies showed a linkage between DPP4 and down-regulation of certain chemokines and mitogenic growth factors, and degradation of denatured collagens (gelatin), suggesting a role of DPP4 in the cell invasive phenotype. Here, we found the existence of a novel protease complex consisting of DPP4 and seprase in human endothelial cells that were activated to migrate and invade in the extracellular matrix in vitro. DPP4 and seprase were coexpressed with the three major protease systems (matrix metalloproteinase, plasminogen activator, and type II transmembrane serine protease) at the cell surface and organize as a complex at invadopodia-like protrusions. Both proteases were colocalized at the endothelial cells of capillaries, but not large blood vessels, in invasive breast ductal carcinoma in vivo. Importantly, monoclonal antibodies against the gelatin-binding domain of DPP4 blocked the local gelatin degradation by endothelial cells in the presence of the major metallo- and serine protease systems that modified pericellular collagenous matrices and subsequent cell migration and invasion. Thus, we have identified a novel mechanism involving the DPP4 gelatin-binding domain of the DPP4-seprase complex that facilitates the local degradation of the extracellular matrix and the invasion of the endothelial cells into collagenous matrices.

Antibodies, Monoclonal↗
PubMed2003

Evidence of a role for Munc18-2 and microtubules in mast cell granule exocytosis.

Compound exocytosis of inflammatory mediators from mast cells requires SNARE and a series of accessory proteins. However, the molecular steps that regulate secretory granule movement and membrane fusion as well as the role of the cytoskeleton are still poorly understood. Here, we report on our investigation of the role of syntaxin-binding Munc18 isoforms and the microtubule network in this process. We found that mast cells express Munc18-2, which interacts with target SNAREs syntaxin 2 or 3, as well as Munc18-3, which interacts with syntaxin 4. Munc18-2 was localised to secretory granules, whereas Munc18-3 was found on the plasma membrane. Increased expression of Munc18-2 and derived peptides containing an interfering effector loop inhibited IgE-triggered exocytosis, while increased expression of Munc18-3 showed no effect. Munc18-2 localisation on granules is polarised; however, upon stimulation Munc18-2 redistributed into forming lamellipodia and persisted on granules that were aligned along microtubules, but was excluded from F-actin ruffles. Disruption of the microtubule network with nocodazole provoked Munc18-2 redistribution and affected mediator release. These findings suggest a role for Munc18-2 and the microtubule network in the regulation of secretory granule dynamics in mast cells.

Actins↗
PubMed1995

Biosynthesis of type VI collagen by glioblastoma cells and possible function in cell invasion of three-dimensional matrices.

The biosynthesis of type VI collagen was studied in human glioblastoma cell line, U-87 MG. The effects of ascorbic acid on type VI collagen synthesis and secretion were investigated. After ascorbic acid treatment, type VI collagen in cell layers increased from 4.48% in control to 6.63% in the ascorbic acid treated cultures, an increase of 48%. The effect of ascorbic acid on type VI collagen synthesized by glioblastoma cells was lower than that reported for osteosarcoma cells (Engvall et al., 1986). The reason for these differences is still under investigation. The function of type VI collagen in glioblastoma cells is still unknown. We utilized the collagen gel system to elucidate the possible roles of type VI collagen in glioblastoma cells in vitro. Glioblastoma cells in collagen gels showed a stellate shape with long, branched processes in all directions. The strong positive reactivity of type VI collagen detected on cell bodies and cell processes by anti-type VI collagen antibody indicated that this specific collagen was associated with cell surfaces and processes, without releasing or diffusing into the gels. Type VI collagen was directly involved in the cell process extension. When living cells were treated with anti-type VI collagen antibody, a variation of cell morphology was observed. Instead of a stellate shape with processes, cells formed clusters without or with very short processes. These data suggest that type VI collagen, synthesized and secreted by glioblastoma cells, may play a role in tumor cell adhesion and spreading, and enhance cell process extension, penetration, and invasion into collagen gels.

Antibodies↗
PubMed2002

Synchronized onset of nuclear and cell surface modifications in U937 cells during apoptosis.

In this study we investigated the relationship between nuclear and cell surface modifications (i.e. blebbing, phosphatidylserine [PS] and sugar residues exposure) in a monocytic cell line, U937, during apoptosis induced by oxidative stress (1 mM H2O2) or inhibition of protein synthesis (10 microg/ml puromycin). Dying cells were simultaneously observed for nuclear modifications, presence of superficial blebs and plasma membrane alterations. Morphological analysis performed by conventional fluorescence microscopy, or by transmission and scanning electron microscopy showed that the courses of nuclear and membrane alterations occured concomitantly, but the phenotype was dependent on the stage of the apoptotic process and the type of apoptogenic inducer used. The progression of apoptosis in U937 cells beyond early stages resulted in the extensive formation of blebs which concomitantly lost some typical markers of apoptosis, such as PS and sugar residues. Therefore, the modality by which the nucleus condenses, or the amount and the pattern of distribution of PS on the cell surface were, for each cell line, strictly related to the apoptogenic inducer. The morphological data reported in the present paper should lead to a more precise quantification of apoptosis by improving the detection of apoptotic cells in vivo (i.e. in tissue, organs), which is a crucial point in the evaluation of efficiency of antiproliferative drugs, such as antiblastic or immunosuppressive compounds.

Apoptosis↗
PubMed2003

Scavenger receptor BI (SR-BI) clustered on microvillar extensions suggests that this plasma membrane domain is a way station for cholesterol trafficking between cells and high-density lipoprotein.

Receptor-mediated trafficking of cholesterol between lipoproteins and cells is a fundamental biological process at the organismal and cellular levels. In contrast to the well-studied pathway of LDL receptor-mediated endocytosis, little is known about the trafficking of high-density lipoprotein (HDL) cholesterol by the HDL receptor, scavenger receptor BI (SR-BI). SR-BI mediates HDL cholesteryl ester uptake in a process in which HDL lipids are selectively transferred to the cell membrane without the uptake and degradation of the HDL particle. We report here the cell surface locale where the trafficking of HDL cholesterol occurs. Fluorescence confocal microscopy showed SR-BI in patches and small extensions of the cell surface that were distinct from sites of caveolin-1 expression. Electron microscopy showed SR-BI in patches or clusters primarily on microvillar extensions of the plasma membrane. The organization of SR-BI in this manner suggests that this microvillar domain is a way station for cholesterol trafficking between HDL and cells. The types of phospholipids in this domain are unknown, but SR-BI is not strongly associated with classical membrane rafts rich in detergent-resistant saturated phospholipids. We speculate that SR-BI is in a more fluid membrane domain that will favor rapid cholesterol flux between the membrane and HDL.

Animals↗
PubMed2006

Ovarian follicle growth in the catfish Iheringichthys labrosus (Siluriformes: Pimelodidae).

The morphofunctional organisation of the female reproductive system, the oocyte growth and the follicular envelope ultrastructure were studied by the first time in the catfish Iheringichthys labrosus from Upper Paraná River basin, Southeastern Brazil, in order to contribute to the knowledge of the reproductive behaviour strategies of this species. As in other Neotropical freshwater siluriforms, the ovaries are of the cystovarian type, the oocytes develop in an asynchronous pattern and mature oocytes are released in clusters in the ovarian lumen, being transported through the oviduct to the urogenital papilla. During the primary growth, nuclear material is transported to the ooplasm, forming the yolk nucleus, where proliferate membranous organelles. The onset of the zona radiata formation occurs during the late perionucleolar stage with the deposition of the outer layer. At the vitellogenic stage, this envelope reaches 6.35+/-0.84microm of thickness, being constituted by three distinct layers crossed by pore-canals containing oocyte and follicular cells processes. Cytochemical analyses evidence neutral glycoproteins in cortical alveoli, yolk globules and zona radiata. Follicular cells with squamous shape during the primary growth acquire synthetic activity at the secondary growth, reaching 37.82+/-4.72mum in height at the mature vitellogenic follicles. These cells accumulate sulphated polysaccharides in large electron-lucent vesicles during the vitellogenic stage which are possibly secreted to form a mucous coat at the egg surface. These evidences suggest that I. labrosus may have adhesive eggs as also detected in other Neotropical freshwater Siluriformes.

Animals↗
PubMed2004

Stimulation-dependent recycling of integrin beta1 regulated by ARF6 and Rab11.

In comparison to the internalization pathways of endocytosis, the recycling pathways are less understood. Even less defined is the process of regulated recycling, as few examples exist and their underlying mechanisms remain to be clarified. In this study, we examine the endocytic recycling of integrin beta1, a process that has been suggested to play an important role during cell motility by mediating the redistribution of integrins to the migrating front. External stimulation regulates the endocytic itinerary of beta1, mainly at an internal compartment that is likely to be a subset of the recycling endosomes. This stimulation-dependent recycling is regulated by ARF6 and Rab11, and also requires the actin cytoskeleton in an ARF6-dependent manner. Consistent with these observations being relevant for cell motility, mutant forms of ARF6 that affect either actin rearrangement or recycling inhibit the motility of a breast cancer cell line.

ADP-Ribosylation Factor 6↗
PubMed2001

Expression of CCR-7, MIP-3beta, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities.

The migration capability of dendritic cells (DCs) is regulated by their response to factors, namely chemokines, that characterize maturation stage and shape their functional activities. This study examines the morphology, expression of chemokines/chemokine receptors, and migration properties of DCs generated after treatment of monocytes with type I interferon (IFN) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (IFN-DCs). IFN-DCs showed phenotypical and morphologic features undetectable in DCs generated in the presence of interleukin 4 (IL-4) and GM-CSF, such as expression of CD83 and CD25 and the presence of CD44+, highly polarized, thin, and long dendrites. IFN-DCs markedly migrated in response to beta-chemokines (especially MIP-1beta) and expressed the Th-1 chemokine IP-10. Notably, IFN-DCs showed an up-regulation of CCR7 as well as of its natural ligand MIP-3beta, characteristics typical of mature DCs. Of interest, IFN-DCs exhibited a marked chemotactic response to MIP-3beta in vitro and strong migratory behavior in severe combined immunodeficient (SCID) mice. In SCID mice reconstituted with human peripheral blood leukocytes, IFN-DCs induced a potent primary human antibody response and IFN-gamma production, indicative of a Th-1 immune response. These results define the highly specialized maturation state of IFN-DCs and point out the existence of a "natural alliance" between type I IFN and monocyte/DC development, instrumental for ensuring an efficient connection between innate and adaptive immunity.

Animals↗
PubMed2004

Cell adhesion to ephrinb2 is induced by EphB4 independently of its kinase activity.

Cell to cell interaction in bone marrow is crucial for differentiation of hematopoietic cells. We have shown that EphB4 receptor is expressed in erythroid progenitor and its activation accelerates erythroid differentiation. To elucidate the role of EphB4 activation in erythropoiesis, we analyzed effects of EphB4 on cell adhesive pathways. Cell adhesion with the extension of filopodial pseudopod was observed by EphB4 activation. EphB4 activation also enhanced an effect of fibronectin-mediated adhesive pathway along with formation of the c-Cbl/CrkL complex. The tyrosine kinase activity of EphB4 was dispensable for those phenomena. These results suggest that activation of EphB4 participates in adhesive but not repulsive signals independently of its tyrosine kinase activity in hematopoietic cells.

Adaptor Proteins, Signal Transducing↗