scholarly journals Integration of the movement of signaling microclusters with cellular motility in immunological synapses

2012 ◽  
Vol 13 (8) ◽  
pp. 787-795 ◽  
Author(s):  
Peter Beemiller ◽  
Jordan Jacobelli ◽  
Matthew F Krummel
Keyword(s):  
Cellular Motility ◽  
Immunological Synapses ◽  
Signaling Microclusters

scholarly journals Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation

2011 ◽  
Vol 195 (5) ◽  
pp. 839-853 ◽  
Author(s):  
Rémi Lasserre ◽  
Céline Cuche ◽  
Ronnie Blecher-Gonen ◽  
Evgeny Libman ◽  
Elise Biquand ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Cell Receptors ◽  
Cell Activation ◽  
Serine Phosphorylation ◽  
Cooperative Binding ◽  
Cell Responses ◽  
Immunological Synapses ◽  
Signaling Microclusters ◽  
The Stability

Antigen recognition within immunological synapses triggers and sustains T cell activation by nucleating protein microclusters that gather T cell receptors (TCRs), kinases, and adaptors. Dissipation of these microclusters results in signal termination, but how this process is regulated is unclear. In this paper, we reveal that release of the adaptors SLP76 and GADS from signaling microclusters is induced by the serine/threonine protein kinase HPK1 and that phosphorylation of GADS plays a major role in this process. We found that HPK1 was recruited into microclusters and triggered their dissipation by inducing the phosphorylation of a threonine-containing motif of GADS, together with the previously described serine phosphorylation of SLP76. These events induced the cooperative binding of 14-3-3 proteins to SLP76–GADS complexes, leading to their uncoupling from the transmembrane adaptor LAT and consequently reducing microcluster persistence and activation-induced gene transcription. These results demonstrate that serine/threonine phosphorylation of multiple TCR-proximal effectors controls the stability of signaling microclusters, thereby determining the intensity of T cell responses.

Synaptic Transmission in the Immune System

e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Jens Rettig ◽  
David R. Stevens
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Neuroendocrine Cells ◽  
Regulated Exocytosis ◽  
Protein Receptor ◽  
Immunological Synapses ◽  
Immunological Diseases

AbstractThe release of neurotransmitters at synapses belongs to the most important processes in the central nervous system. In the last decades much has been learned about the molecular mechanisms which form the basis for this fundamental process. Highly regulated exocytosis, based on the SNARE (soluble N-ethylmaleimide-sensitive attachment protein receptor) complex and its regulatory molecules is the signature specialization of the nervous system and is shared by neurons and neuroendocrine cells. Cells of the immune system use a similar mechanism to release cytotoxic materials from secretory granules at contacts with virally or bacterially infected cells or cancer cells, in order to remove these threats. These contact zones have been termed immunological synapses in reference to the highly specific targeted exocytosis of effector molecules. Recent findings indicate that mutations in SNARE or SNARE-interacting proteins are the basis of a number of devastating immunological diseases. While SNARE complexes are ubiquitous and mediate a wide variety of membrane fusion events it is surprising that in many cases the SNARE proteins involved in immunological synapses are the same molecules which mediate regulated exocytosis of transmitters and hormones in neurons and neuroendocrine cells. These similarities raise the possibility that results obtained at immunological synapses may be applicable, in particular in the area of presynaptic function, to neuronal synapses. Since immunological synapses (IS) are assembled and disassembled in about a half an hour, the use of immune cells isolated from human blood allows not only the study of the molecular mechanisms of synaptic transmission in human cells, but is particularly suited to the examination of the assembly and disassembly of these “synapses” via live imaging. In this overview we discuss areas of similarity between synapses of the nervous and immune systems and in the process will refer to results of our experiments of the last few years.

scholarly journals Androgen receptor and chemokine receptors 4 and 7 form a signaling axis to regulate CXCL12-dependent cellular motility

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Jordy J Hsiao ◽  
Brandon H Ng ◽  
Melinda M Smits ◽  
Jiahui Wang ◽  
Rohini J Jasavala ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Chemokine Receptors ◽  
Cellular Motility ◽  
Signaling Axis

scholarly journals A Decade of Imaging Cellular Motility and Interaction Dynamics in the Immune System

Science ◽  
2012 ◽  
Vol 336 (6089) ◽  
pp. 1676-1681 ◽  
Author(s):  
Ronald N. Germain ◽  
Ellen A. Robey ◽  
Michael D. Cahalan
Keyword(s):  
Lymph Nodes ◽  
Live Cell Imaging ◽  
Quantitative Measurement ◽  
Cell Imaging ◽  
Plasma Cells ◽  
Effector T Cells ◽  
Cellular Interactions ◽  
Cellular Motility ◽  
Response Dynamics

To mount an immune response, lymphocytes must recirculate between the blood and lymph nodes, recognize antigens upon contact with specialized presenting cells, proliferate to expand a small number of clonally relevant lymphocytes, differentiate to antibody-producing plasma cells or effector T cells, exit from lymph nodes, migrate to tissues, and engage in host-protective activities. All of these processes involve motility and cellular interactions—events that were hidden from view until recently. Introduced to immunology by three papers in this journal in 2002, in vivo live-cell imaging studies are revealing the behavior of cells mediating adaptive and innate immunity in diverse tissue environments, providing quantitative measurement of cellular motility, interactions, and response dynamics. Here, we review themes emerging from such studies and speculate on the future of immunoimaging.

scholarly journals Modulation of Cellular Migration and Survival by c-Myc through the Downregulation of Urokinase (uPA) and uPA Receptor

2010 ◽  
Vol 30 (7) ◽  
pp. 1838-1851 ◽  
Author(s):  
Daniela Alfano ◽  
Giuseppina Votta ◽  
Almut Schulze ◽  
Julian Downward ◽  
Mario Caputi ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Epithelial Cell Line ◽  
Cellular Motility ◽  
Upa Receptor ◽  
Upar Expression ◽  
Repressive Effect ◽  
Cell Invasiveness

ABSTRACT It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness.

Motility of the Limulus blood cell

1979 ◽  
Vol 37 (1) ◽  
pp. 169-180
Author(s):  
P.B. Armstrong
Keyword(s):  
Tissue Culture ◽  
Time Lapse ◽  
Coelomic Fluid ◽  
Cellular Motility ◽  
Paraffin Oil ◽  
Motile Cells ◽  
Direct Microscopic Examination ◽  
High Concentrations ◽  
Glass Surfaces

The sole cell type (the amoebocyte) found in the coelomic fluid of the horseshoe crab, Limulus polyphemus can be stimulated to become motile by extravasation or trauma. Motility was studied using time-lapse microcinematography and direct microscopic examination of cells in tissue culture and in gill leaflets isolated from young animals. Phase-contrast and Nomarski differential-interference contrast optics were employed. Both in culture and in the gills, motile cells showed 2 interconvertible morphological types: the contracted cell, which was compact and rounded and had a relatively small area of contact with the substratum, and a flattened from with a larger area of contact. In both morphological types, motility involved the protrusion of hyaline pseudopods followed by flow of granular endoplasm forward in the pseudoplod. Cellular motility in vivo (in the gill leaflet) was morphologically identical to that displayed in tissue culture. In culture, motility was unaffected by the nature of the substratum: cells were indistinguishable on fluid (paraffin oil) or solid (glass) substrata or on hydrophobic (paraffin oil, siliconized glass) or hydrophilic (clean glass) surfaces. Cells migrated and spread on agar surfaces. Cell motility was unaffected by high concentrations (100 micrograms/ml) of the microtubule-depolymerizing agent colcemid and was abolished by cytochalasin B at 1 microgram/ml.

Effects of Cytochalasins on the Initial Aggregation in Vitro of Embryonic Chick Cells

1974 ◽  
Vol 14 (1) ◽  
pp. 187-196
Author(s):  
J. C. APPLETON ◽  
R. B. KEMP
Keyword(s):  
Cytochalasin B ◽  
Cell Aggregation ◽  
Cellular Injury ◽  
Cellular Motility ◽  
Carbon Dioxide Evolution ◽  
Site Of Action ◽  
Dissociated Cells ◽  
Cytochalasin A ◽  
Final Confirmation

The initial aggregation of trypsin-dissociated cells from the skeletal muscle tissue of 9-day-old chick embryos in the presence of cytochalasins A and B was studied in order to discover the effects of these agents on contact and adhesion. Cytochalasin B (3 µg/ml) had a negligible effect on the rate of aggregation of cells over an 8-h period, but cytochalasin A at concentrations between 3 and 20 µg/ml markedly inhibited aggregation. Both agents altered the shape and size of aggregates and caused cells at their periphery to appear more spherical. The oxygen uptake of the treated cells was not noticeably different from that of the controls, despite the severe inhibition of isotopic carbon dioxide evolution. The effect of cytochalasin B on cell aggregation was reversible and although the cytochalasin A effect could not be abolished on return to medium free of A, the unaltered oxygen consumption was taken as an indication that permanent cellular injury did not occur. The effect of the cytochalasins on aggregate structure was interpreted on the basis of arrested cellular motility, but the singular inhibition by cytochalasin A of the rate of aggregation must await final confirmation of its site of action.

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