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Results for “Cell Surface Extensions”

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At least 181 records · Page 10Linked to original sources

PubMed1983

Universal rosetting reagent for the detection of human cell surface markers.

The extensive use of monoclonal antibodies for the detection of human cell surface markers has necessitated the development of a simple, reproducible reagent which can be applied universally to any mouse anti-human antibody. We have developed a rosetting reagent which is composed of ox red blood cells, rabbit anti-ox RBC antibody, protein A, and rabbit anti-mouse Ig antibody. This reagent binds specifically to human lymphocytes coated with mouse monoclonal antibody, is as sensitive as immunofluorescence and gives comparable results with fresh and frozen peripheral blood lymphocytes. Sensitivity, reliability, and ease of quantitation make this an extremely practical reagent, and its versatility makes it especially useful for large scale studies of human T cell markers.

Animals↗

PubMed2003

Rapid and extensive membrane reorganization by dendritic cells following exposure to bacteria revealed by high-resolution imaging.

Using live cell imaging, we demonstrate that immature dendritic cells (DC) derived from human peripheral blood monocytes undergo pronounced morphologic changes in vitro within minutes of exposure to unopsonized Escherichia coli, developing extensive membrane veils that efficiently capture additional bacteria. Internalization does not occur in the veils, but instead, bacteria are transported to the central region of the cell, where they sink directly into the plasma membrane. In contrast, exposure to polystyrene beads does not induce notable changes in cell morphology, and DC do not efficiently capture beads when introduced alone or mixed with bacteria. Long dendritic processes were also visualized in some cells that allowed capture of clumps of bacteria at a distance of more than 100 microm. These results demonstrate that immature DC can distinguish between inert particles and bacteria and alter their shape and phagocytic capacity in response to the latter.

Cell Membrane↗

PubMed2003

Identification of a new mechanism for bacterial uptake at mucosal surfaces, which is mediated by dendritic cells.

Dendritic cells are potent activators of the immune response. They reside in tissues which interface the external environment, but we shall see that they do not perform only a passive role by monitoring microorganisms that have entered the body. Rather, DC can actively participate to microbial entry across mucosal surfaces by creeping between epithelial cells and by internalizing bacteria via their dendrites.

Animals↗

PubMed2003

Podosomes: adhesion hot-spots of invasive cells.

Podosomes are highly dynamic, actin-rich adhesion structures of monocyte-derived cells, certain transformed fibroblasts and carcinoma cells and have recently also been discovered in an increasing number of other cell types. Because they are found mainly in motile cells and control the activity of matrix metalloproteases, podosomes are thought to contribute to tissue invasion and matrix remodeling. Importantly, podosomes are physiologically relevant organelles because they can be found in ex vivo models of invasive cells. Regulators of podosome turnover include tyrosine kinases, RhoGTPases, actin regulators and the microtubule system. Podosomes might also serve as an attractive model to study how integration of various signaling pathways controls actin dynamics. Here, we summarize and discuss the known structural, regulatory and functional features of podosomes, our aim being to stimulate further research into these unique structures.

Actin Cytoskeleton↗

PubMed2005

The pro-inflammatory mediator leukotriene D4 induces phosphatidylinositol 3-kinase and Rac-dependent migration of intestinal epithelial cells.

Inflammatory bowel diseases are associated with increased risk of developing colon cancer. A possible role of the pro-inflammatory leukotriene D4 (LTD4) in this process has been implicated by the findings that LTD4 can signal increased proliferation and survival, both hallmarks of a cancer cell, in non-transformed intestinal epithelial cells. Here we make the novel finding that LTD4 can also signal increased motility in these cells. In parallel, we found that LTD4 induced a simultaneous transient 10-fold increase in Rac but not Cdc42 activity. These data were also supported by the ability of LTD4 to activate the Rac GDP/GTP exchange factor Vav2. Further, LTD4 triggered a 3-fold transient increase in phosphatidylinositol 3-kinase (PI3K) phosphorylation, a possible upstream activator of the Vav2/Rac signaling pathway. The activation of Rac was blocked by the PI3K inhibitors LY294002 and wortmannin and by transfection of a kinase-negative mutant of PI3K or a dominant-negative form of Vav2. Furthermore, Rac was found to co-localize with actin in LTD4-generated membrane ruffles that were formed by a PI3K-dependent mechanism. In accordance, the inhibition of the PI3K and Rac signaling pathway also blocked the LTD4-induced migration of the intestinal cells. The present data reveal that an inflammatory mediator such as LTD4 cannot only increase proliferation and survival of non-transformed intestinal epithelial cells but also, via a PI3K/Rac signaling pathway, trigger a motile response in such cells. These data demonstrate the capacity of inflammatory mediators to participate in the process by which inflammatory bowel conditions increase the risk for colon cancer development.

Actins↗

PubMed2002

Yersinia type III secretion: send in the effectors.

Pathogenic Yersinia spp (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) have evolved an exquisite method for delivering powerful effectors into cells of the host immune system where they inhibit signaling cascades and block the cells' response to infection. Understanding the molecular mechanisms of this system has provided insight into the processes of phagocytosis and inflammation.

Adhesins, Bacterial↗

PubMed2005

Long-distance calls between cells connected by tunneling nanotubules.

Long membrane tethers between cells, known as membrane nantotubes or tunneling nanotubules, create supracellular structures that allow multiple cell bodies to act in a synchronized manner. Calcium fluxes, vesicles, and cell-surface components can all traffic between cells connected by nanotubes. Thus, complex and specific messages can be transmitted between multiple cells, and the strength of signal will suffer relatively little with the distance traveled, as compared to the use of soluble factors to transmit messages. Connecting multiple antigen-presenting cells, for example, can help amplify and coordinate immune responses that are distal to an antigenic site. Conversely, because the ability of a pathogen to spread between cells is a key determinant of its capacity to multiply, pathogens may exploit nanotubes for their own transmission.

Animals↗

PubMed2006

A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation.

Dendritic cells (DCs) are professional APCs of the immune system that play a key role in regulating T cell-based immunity. The capacity of DCs to activate T cells depends on their maturation state as well as their ability to migrate to the T cell areas of draining lymph nodes. In this study, we investigated the effects of DC maturation stimuli on the actin cytoskeleton and beta(1) integrin-dependent adhesion and migration. Podosomes, specialized adhesion structures found in immature monocyte-derived DCs as well as myeloid DCs, rapidly dissolve in response to maturation stimuli such as TNF-alpha and PGE(2), whereas the TLR agonist LPS induces podosome dissolution only after a long lag time. We demonstrate that LPS-mediated podosome disassembly as well as the onset of high-speed DC migration are dependent on the production of PGs by the DCs. Moreover, both of these processes are inhibited by Ab-induced activation of beta(1) integrins. Together, these results show that maturation-induced podosome dissolution and loss of alpha(5)beta(1) integrin activity allow human DCs to undergo the transition from an adhesive to a highly migratory phenotype.

Cell Adhesion↗

PubMed2006

The Src homology 2 domain-containing leukocyte protein of 76-kDa adaptor links integrin ligation with p44/42 MAPK phosphorylation and podosome distribution in murine dendritic cells.

The Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) is an important molecular intermediate in multiple signaling pathways governing immune cell function. In this study, we report that SLP-76 is expressed in CD11c+ B220- dendritic cells (DCs) isolated from murine thymus or spleen, and that SLP-76 is rapidly phosphorylated on tyrosine residues upon plating of bone marrow-derived DCs (BMDCs) on integrin agonists. SLP-76 is not required for the in vitro or in vivo generation of DCs, but SLP-76-deficient BMDCs adhere poorly to fibronectin, suggesting impaired integrin function. Consistent with impaired adhesion, cutaneous SLP-76-deficient DCs leave ear tissue at an elevated frequency compared with wild-type DCs. In addition, the pattern and distribution of actin-based podosome formation are visibly altered in BMDCs lacking SLP-76 following integrin engagement. SLP-76-deficient BMDCs manifest multiple signaling defects following integrin ligation, including reduced global tyrosine phosphorylation and markedly impaired phosphorylation of p44/42 MAPK (ERK1/2). These data implicate SLP-76 as an important molecular intermediate in the signaling pathways regulating multiple integrin-dependent DC functions, and add to the growing body of evidence that hemopoietic cells may use unique molecular intermediates and mechanisms for regulating integrin signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming.

Upon maturation, dendritic cells (DCs) acquire the unique ability to activate naïve T cells. We used time-lapse video microscopy and two-photon imaging of intact lymph nodes to show that after establishing initial contact between their dendrites and naïve T lymphocytes, mature DCs migrate toward the contacted lymphocytes. Subsequently, the DCs tightly entrap the T cells within a complex net of membrane extensions. The Rho family guanosine triphosphatases Rac1 and Rac2 but not Rho itself control the formation of dendrites in mature DCs, their polarized short-range migration toward T cells, and T cell priming.

Animals↗

PubMed2005

Receptor tyrosine phosphatase-dependent cytoskeletal remodeling by the hedgehog-responsive gene MIM/BEG4.

During development, dynamic remodeling of the actin cytoskeleton allows the precise placement and morphology of tissues. Morphogens such as Sonic hedgehog (Shh) and local cues such as receptor protein tyrosine phosphatases (RPTPs) mediate this process, but how they regulate the cytoskeleton is poorly understood. We previously identified Basal cell carcinoma-enriched gene 4 (BEG4)/Missing in Metastasis (MIM), a Shh-inducible, Wiskott-Aldrich homology 2 domain-containing protein that potentiates Gli transcription (Callahan, C.A., T. Ofstad, L. Horng, J.K. Wang, H.H. Zhen, P.A. Coulombe, and A.E. Oro. 2004. Genes Dev. 18:2724-2729). Here, we show that endogenous MIM is induced in a patched1-dependent manner and regulates the actin cytoskeleton. MIM functions by bundling F-actin, a process that requires self-association but is independent of G-actin binding. Cytoskeletal remodeling requires an activation domain distinct from sequences required for bundling in vitro. This domain associates with RPTPdelta and, in turn, enhances RPTPdelta membrane localization. MIM-dependent cytoskeletal changes can be inhibited using a soluble RPTPdelta-D2 domain. Our data suggest that the hedgehog-responsive gene MIM cooperates with RPTP to induce cytoskeletal changes.

Actins↗

PubMed1995

Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin.

P-selectin is a Ca(2+)-dependent lectin that participates in leukocyte adhesion to vascular endothelium and platelets. Myeloid cells and a subset of T lymphocytes express carbohydrate ligands at the cell surface. Previously, we suggested that heat stable antigen (HSA/mouse CD24), an extensively glycosylated cell surface molecule on many mouse cells, is a ligand for P-selectin. Here we show that HSA mediates the binding of monocytic cells and neutrophils to P-selectin. The monocytic cell lines ESb-MP and J774, peritoneal exudate cells, and bone marrow neutrophils could bind to lipopolysaccharide-activated bend3 endothelioma cells under rotation-induced shear forces and this binding was inhibited by mAb to P-selectin and HSA. Blocking was weak at room temperature but more efficient at 4 degrees C when integrin-mediated binding was decreased. Also the adhesion of neutrophils to stimulated platelets expressing P-selectin was blocked by HSA- and P-selectin-specific mAb. Latex beads coated with purified HSA from myeloid cells bound to activated endothelioma cells or platelets, and the binding was similarly blocked by mAb to P-selectin and HSA respectively. The HSA-coated beads were stained with P-selectin-IgG, very weakly with L-selectin-IgG but not with E-selectin-IgG. The staining was dependent on divalent cations and treatment with endoglycosidase F or neuraminidase indicated that sialylated N-linked glycans were recognized. The presence of these glycans was confirmed by biosynthetic labeling studies. Our data suggest that HSA, in addition to the recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to a group of monospecific P-selectin ligands on myeloid cells.

Animals↗

PubMed2004

Uterine receptivity and the plasma membrane transformation.

This review begins with a brief commentary on the diversity of placentation mechanisms, and then goes on to examine the extensive alterations which occur in the plasma membrane of uterine epithelial cells during early pregnancy across species. Ultrastructural, biochemical and more general morphological data reveal that strikingly common phenomena occur in this plasma membrane during early pregnancy despite the diversity of placental types--from epitheliochorial to hemochorial, which ultimately form in different species. To encapsulate the concept that common morphological and molecular alterations occur across species, that they are found basolaterally as well as apically, and that moreover they are an ongoing process during much of early pregnancy, not just an event at the time attachment, the term 'plasma membrane transformation' is suggested which also emphasises that alterations in this plasma membrane during early pregnancy are key to uterine receptivity.

Animals↗

PubMed2003

Dynamin at the actin-membrane interface.

Many important cellular processes such as phagocytosis, cell motility and endocytosis require the participation of a dynamic and interactive actin cytoskeleton that acts to deform cellular membranes. The extensive family of non-traditional myosins has been implicated in linking the cortical actin gel with the plasma membrane. Recently, however, the dynamins have also been included in these cell processes as a second family of mechanochemical enzymes that self-associate and hydrolyze nucleotides to perform 'work' while linking cellular membranes to the actin cytoskeleton. The dynamins are believed to form large helical polymers from which extend many interactive proline-rich tail domains, and these domains bind to a variety of SH3-domain-containing proteins, many of which appear to be actin-binding proteins. Recent data support the concept that the dynamin family might act as a 'polymeric contractile scaffold' at the interface between biological membranes and filamentous actin.

Actin Cytoskeleton↗

PubMed2005

Distinction at the leading edge of the cell.

Cell locomotion is governed by spatially and temporally co-ordinated changes in the organization of the actin cytoskeleton. In the highlighted manuscript,((1)) the authors focus on actin remodelling at the front of moving cells to reveal the existence of two distinct yet spatially overlapping actin networks that play largely independent yet fundamental roles in cell migration. The first is defined as the lamellipodium, which assembles and disassembles within the first 3 microm of the leading edge. This serves to promote the random protrusion and retraction of the leading edge but has no role in productive cell translocation. The second actin network, the lamella, is responsible for the advancement of the cell by integrating contraction with cellular adhesions.

Actins↗

PubMed2006

Type III secretion, contact-dependent model for the intracellular development of chlamydia.

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design.

Algorithms↗

PubMed2006

Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells.

Polarity is a central feature of eukaryotic cells and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) has a central role in the polarization of neurons and chemotaxing cells. In polarized epithelial cells, PtdIns(3,4,5)P3 is stably localized at the basolateral plasma membrane, but excluded from the apical plasma membrane, as shown by localization of GFP fused to the PtdIns(3,4,5)P3-binding pleckstrin-homology domain of Akt (GFP-PH-Akt), a fusion protein that indicates the location of PtdIns(3,4,5)P3. Here, we ectopically inserted exogenous PtdIns(3,4,5)P3 into the apical plasma membrane of polarized Madin-Darby canine kidney (MDCK) cells. Within 5 min many cells formed protrusions that extended above the apical surface. These protrusions contained basolateral plasma membrane proteins and excluded apical proteins, indicating that their plasma membrane was transformed from apical to basolateral. Addition of PtdIns(3,4,5)P3 to the basolateral surface of MDCK cells grown as cysts caused basolateral protrusions. MDCK cells grown in the presence of a phosphatidylinositol 3-kinase inhibitor had abnormally short lateral surfaces, indicating that PtdIns(3,4,5)P3 regulates the formation of the basolateral surface.

Animals↗

PubMed2005

Coupling the dynamics of two actin networks--new views on the mechanics of cell protrusion.

We study how mechanical forces integrate spatially and temporally with regulatory signals at the leading edge of migrating cells. To probe the dynamics of this system, we developed quantitative fluorescent speckle microscopy, which maps out actin cytoskeleton transport, assembly and disassembly with high spatial resolution. Statistical processing of single speckle properties revealed two kinetically, kinematically and molecularly distinct, yet spatially overlapping, actin arrays at the leading edge of migrating epithelial cells. The first network, referred to as the lamellipodium, polymerizes and depolymerizes 1-2 microm from the edge in an Arp2/3 (actin-related protein 2/3)- and cofilin-dependent fashion. The second network, referred to as the lamella, exhibits Arp2/3-independent polymerization. To elucidate the dynamic relationship between the two networks, we have begun to examine how assembly and flow are temporally modulated with respect to a protrusion event. In control cells we found bursts of protrusion preceding bursts of F-actin assembly. The time lag disappears in cells where Arp2/3-function is impaired. This and other results allowed us to propose a model in which tropomyosin protects lamella filaments from branching and severing, and to conjecture that Arp2/3-mediated lamellipodium assembly is a natural consequence of lamella expansion, but not the initiator of cell protrusion.

Actins↗