scholarly journals A direct role for SNX9 in the biogenesis of filopodia

2019 ◽  
Author(s):  
IK Jarsch ◽  
JR Gadsby ◽  
A Nuccitelli ◽  
J Mason ◽  
H Shimo ◽  
...  
Keyword(s):  
Cell Surface ◽  
Phage Display ◽  
Cell Communication ◽  
Phenotypic Screening ◽  
Direct Role ◽  
Transient Nature ◽  
Endogenous Component ◽  
Antibody Technology ◽  
Cell Cell

SummaryFilopodia are finger-like actin-rich protrusions that extend from the cell surface and are important for cell-cell communication and pathogen internalization. The small size and transient nature of filopodia combined with shared usage of actin regulators within cells confounds attempts to identify filopodial proteins. Here, we used phage display phenotypic screening to isolate antibodies that alter the actin morphology of filopodia-like structures in vitro. We found that all of the antibodies that cause shorter FLS interact with SNX9, an actin regulator that binds phosphoinositides during endocytosis and in invadopodia. In cells, we discover SNX9 at specialised filopodia in Xenopus development and that SNX9 is an endogenous component of filopodia that are hijacked by Chlamydia entry. We show the use of antibody technology to identify proteins used in filopodia-like structures, and a role for SNX9 in filopodia.

scholarly journals A direct role for SNX9 in the biogenesis of filopodia

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Iris K. Jarsch ◽  
Jonathan R. Gadsby ◽  
Annalisa Nuccitelli ◽  
Julia Mason ◽  
Hanae Shimo ◽  
...  
Keyword(s):  
Cell Surface ◽  
Phage Display ◽  
Cell Communication ◽  
Phenotypic Screening ◽  
Direct Role ◽  
Xenopus Development ◽  
Transient Nature ◽  
Endogenous Component ◽  
Antibody Technology

Filopodia are finger-like actin-rich protrusions that extend from the cell surface and are important for cell–cell communication and pathogen internalization. The small size and transient nature of filopodia combined with shared usage of actin regulators within cells confounds attempts to identify filopodial proteins. Here, we used phage display phenotypic screening to isolate antibodies that alter the actin morphology of filopodia-like structures (FLS) in vitro. We found that all of the antibodies that cause shorter FLS interact with SNX9, an actin regulator that binds phosphoinositides during endocytosis and at invadopodia. In cells, we discover SNX9 at specialized filopodia in Xenopus development and that SNX9 is an endogenous component of filopodia that are hijacked by Chlamydia entry. We show the use of antibody technology to identify proteins used in filopodia-like structures, and a role for SNX9 in filopodia.

scholarly journals TGF-β1 facilitates cell–cell communication in osteocytes via connexin43- and pannexin1-dependent gap junctions

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Wenjing Liu ◽  
Demao Zhang ◽  
Xin Li ◽  
Liwei Zheng ◽  
Chen Cui ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Lucifer Yellow ◽  
Cell Communication ◽  
Deep Understanding ◽  
Gap Junctional Intercellular Communication ◽  
Tgf Β1 ◽  
Cell Cell

Abstract Connexins and pannexins are two families of channel forming proteins that are able to pass small molecules to achieve communication between cells. While connexins have been recognized to mediate gap junctional intercellular communication (GJIC), pannexins are far less known. Our previous study reported the potential role of TGF-β1 in mediating of connexins in osteocytes in vitro. Herein, we aimed to elucidate the influence of TGF-β1 on cell–cell communication based on gap junctions assembled by connexins and pannexins in vitro and ex vivo. We first showed that TGF-β1 positively affected the elongation of dendritic processes of osteocytes. Our data indicated that TGF-β1 increased expressions of connexin43 (Cx43) and pannexin1 (panx1), which are indispensable for hemichannel formation in gap junctions, in osteocytes in vitro and ex vivo. TGF-β1 enhanced gap junction formation and impacted cell–cell communication in living osteocytes, as indicated by the scrape loading and Lucifer yellow transfer assays. TGF-β1 enhanced the expressions of Cx43 and panx1 via activation of ERK1/2 and Smad3/4 signalling. The TGF-β1-restored expressions of Cx43 and panx1 in osteocytes in the presence of an ERK inhibitor, U0126, further demonstrated the direct participation of Smad3/4 signalling. TGF-β1 increased the accumulation of Smad3 in the nuclear region (immunofluorescence assay) and promoted the enrichment of Smad3 at the binding sites of the promoters of Gja1 (Cx43) and Panx1 (ChIP assay), thereby initiating the enhanced gene expression. These results provide a deep understanding of the molecular mechanisms involved in the modulation of cell–cell communication in osteocytes induced by TGF-β1.

scholarly journals IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart

2009 ◽  
Vol 296 (5) ◽  
pp. H1694-H1704 ◽  
Author(s):  
Indroneal Banerjee ◽  
John W. Fuseler ◽  
Arti R. Intwala ◽  
Troy A. Baudino
Keyword(s):  
Cardiac Function ◽  
Cardiac Fibroblasts ◽  
Cell Communication ◽  
Cell Types ◽  
Capillary Density ◽  
Cell Populations ◽  
Cardiac Cell ◽  
Altered Expression ◽  
Cell Cell

Interleukin-6 (IL-6) is a pleiotropic cytokine responsible for many different processes including the regulation of cell growth, apoptosis, differentiation, and survival in various cell types and organs, including the heart. Recent studies have indicated that IL-6 is a critical component in the cell-cell communication between myocytes and cardiac fibroblasts. In this study, we examined the effects of IL-6 deficiency on the cardiac cell populations, cardiac function, and interactions between the cells of the heart, specifically cardiac fibroblasts and myocytes. To examine the effects of IL-6 loss on cardiac function, we used the IL-6 −/− mouse. IL-6 deficiency caused severe cardiac dilatation, increased accumulation of interstitial collagen, and altered expression of the adhesion protein periostin. In addition, flow cytometric analyses demonstrated dramatic alterations in the cardiac cell populations of IL-6 −/− mice compared with wild-type littermates. We observed a marked increase in the cardiac fibroblast population in IL-6 −/− mice, whereas a concomitant decrease was observed in the other cardiac cell populations examined. Moreover, we observed increased cell proliferation and apoptosis in the developing IL-6 −/− heart. Additionally, we observed a significant decrease in the capillary density of IL-6 −/− hearts. To elucidate the role of IL-6 in the interactions between cardiac fibroblasts and myocytes, we performed in vitro studies and demonstrated that IL-6 deficiency attenuated the activation of the STAT3 pathway and VEGF production. Taken together, these data demonstrate that a loss of IL-6 causes cardiac dysfunction by shifting the cardiac cell populations, altering the extracellular matrix, and disrupting critical cell-cell interactions.

scholarly journals A model system for cell adhesion and signal transduction in Drosophila

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 163-176 ◽  
Author(s):  
Mark Peifer ◽  
Sandra Orsulic ◽  
Li-Mei Pai ◽  
Joseph Loureiro
Keyword(s):  
Cell Adhesion ◽  
Function Analysis ◽  
Cell Communication ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Direct Role ◽  
Junction Protein ◽  
Wingless Signaling ◽  
Segment Polarity ◽  
Cell Cell

Cells must cooperate and communicate to form a multicellular animal. Information about the molecules required for these processes have come from a variety of sources; the convergence between the studies of particular molecules by vertebrate cell biologists and the genes identified by scientists investigating development in Drosophila has been especially fruitful. We are interested in the connection between cadherin proteins that regulate cell-cell adhesion and the wingless/wnt-1 cell-cell signaling molecules controlling pattern formation during development. The Drosophila segment polarity gene armadillo, homolog of the vertebrate adherens junction protein-catenin, is required for both cell adhesion and wg signaling. We review what is known about wingless signaling in Drosophila, and discuss the role of cell-cell junctions in both cell adhesion and cell communication. We then describe the results of our preliminary structure-function analysis of Armadillo protein in both cell adhesion and wingless signaling. Finally, we discuss evidence supporting a direct role for Armadillo and adherens junction in transduction of wingless signal.

scholarly journals Enhanced Waddington landscape model with cell–cell communication can explain molecular mechanisms of self-organization

2019 ◽  
Vol 35 (20) ◽  
pp. 4081-4088
Author(s):  
Hosein Fooladi ◽  
Parsa Moradi ◽  
Ali Sharifi-Zarchi ◽  
Babak Hosein Khalaj
Keyword(s):  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Cell Communication ◽  
Self Organization ◽  
Supplementary Information ◽  
Embryonic Cells ◽  
Human Escs ◽  
Germ Layers ◽  
Cell Cell

Abstract Motivation The molecular mechanisms of self-organization that orchestrate embryonic cells to create astonishing patterns have been among major questions of developmental biology. It is recently shown that embryonic stem cells (ESCs), when cultured in particular micropatterns, can self-organize and mimic the early steps of pre-implantation embryogenesis. A systems-biology model to address this observation from a dynamical systems perspective is essential and can enhance understanding of the phenomenon. Results Here, we propose a multicellular mathematical model for pattern formation during in vitro gastrulation of human ESCs. This model enhances the basic principles of Waddington epigenetic landscape with cell–cell communication, in order to enable pattern and tissue formation. We have shown the sufficiency of a simple mechanism by using a minimal number of parameters in the model, in order to address a variety of experimental observations such as the formation of three germ layers and trophectoderm, responses to altered culture conditions and micropattern diameters and unexpected spotted forms of the germ layers under certain conditions. Moreover, we have tested different boundary conditions as well as various shapes, observing that the pattern is initiated from the boundary and gradually spreads towards the center. This model provides a basis for in-silico modeling of self-organization. Availability and implementation https://github.com/HFooladi/Self_Organization. Supplementary information Supplementary data are available at Bioinformatics online.

Mechanisms for de novo biogenesis of an apical membrane compartment in groups of simple epithelial cells surrounded by extracellular matrix

1997 ◽  
Vol 110 (22) ◽  
pp. 2781-2794 ◽  
Author(s):  
G.K. Ojakian ◽  
W.J. Nelson ◽  
K.A. Beck
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Golgi Complex ◽  
De Novo ◽  
Apical Membrane ◽  
Free Cell ◽  
Cell Contacts ◽  
Lateral Membrane ◽  
Cell Cell

In open monolayers of epithelial cells grown in vitro, the apical membrane domain forms on the free cell surface that faces the culture medium. However, in vivo, the apical lumenal compartment arises within groups of cells that do not have a free cell surface. We designed in vitro culture conditions, using small colonies of MDCK cells overlaid with collagen, in which formation of the apical membrane must occur de novo by remodeling existing membrane domains that are contacted by other cells or extracellular matrix. Within 12 hours of collagen overlay, the apical membrane glycoprotein gp135 is removed from the free cell surface, while lateral membrane proteins (e.g. Na+,K+-ATPase) remain at sites of cell-cell contacts. Subsequently, lumenal structures, containing gp135 and the apically secreted protein gp81, formed within these cell-cell contacts. Na+,K+-ATPase, adherens junction (E-cadherin, alpha- and beta-catenins) and tight junction (ZO-1) proteins were localized on the lateral membrane adjacent to, but excluded from the gp135-positive lumenal compartment. Therefore, each lumen represents a newly formed apical compartment on the lateral membrane. The Golgi complex (alpha-mannosidase II and Golgi beta-spectrin), centrosomes (gamma-tubulin) and microtubules reorient to a cytoplasmic position adjacent to the newly-forming apical lumenal compartments. Significantly, addition of colchicine, nocodazole or brefeldin A inhibits apical lumen formation. These results demonstrate that simple epithelial cells form an apical lumenal compartment de novo through initial intermixing, and then sorting of apical and basal-lateral membrane proteins at sites of cell-cell contacts. In addition, apical lumen formation requires an intact microtubule network, microtubule-dependent reorientation of the Golgi complex and secretory apparatus, and fully functional protein delivery from the Golgi complex to the forming apical cell surface.

Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2173-2179 ◽  
Author(s):  
Martha J. James ◽  
Lavina Belaramani ◽  
Kanella Prodromidou ◽  
Arpita Datta ◽  
Sussan Nourshargh ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Interactions ◽  
Cell Surface Expression ◽  
Anergic T Cells ◽  
Parenchymal Cells ◽  
Cell Cell

Abstract Due to their ability to inhibit antigen-induced T-cell activation in vitro and in vivo, anergic T cells can be considered part of the spectrum of immunoregulatory T lymphocytes. Here we report that both murine and human anergic T cells can impair the ability of parenchymal cells (including endothelial and epithelial cells) to establish cell-cell interactions necessary to sustain leukocyte migration in vitro and tissue infiltration in vivo. The inhibition is reversible and cell-contact dependent but does not require cognate recognition of the parenchymal cells to occur. Instrumental to this effect is the increased cell surface expression and enzymatic activity of molecules such as CD26 (dipeptidyl-peptidase IV), which may act by metabolizing chemoattractants bound to the endothelial/epithelial cell surface. These results describe a previously unknown antigen-independent anti-inflammatory activity by locally generated anergic T cells and define a novel mechanism for the long-known immunoregulatory properties of these cells.

P14. Gap junctions between osteoblast-like cells in vitro: A model to study cell-cell-communication

Bone ◽  
1994 ◽  
Vol 15 (1) ◽  
pp. 120
Author(s):  
K Schirrmacher ◽  
E Winterhager ◽  
O Traub ◽  
F Brummer ◽  
D Jones ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Cell Communication ◽  
Cell Cell
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