scholarly journals Regulation of urokinase receptor function and pericellular proteolysis by the integrin α5β1

2009 ◽  
Vol 101 (05) ◽  
pp. 954-962 ◽  
Author(s):  
Rosemary Bass ◽  
Vincent Ellis
Keyword(s):  
Cell Adhesion ◽  
Cell Types ◽  
Dependent Manner ◽  
Integrin Α5β1 ◽  
Upa Receptor ◽  
Cellular Localisation ◽  
Dependent Cell ◽  
Invasive Cell ◽  
Pericellular Proteolysis

SummaryInteractions between the uPA receptor (uPAR) and various inte-grins, including α5β1, are known to modulate integrin-dependent cell adhesion, and we have shown that the integrin-associated tetraspanin protein CD82 down-regulates uPAR-dependent plasminogen activation by affecting α5β1 cellular localisation. Here we have investigated whether overexpression of α5β1 directly affects uPAR-dependent pericellular proteolysis. CHO cells overexpressing α5β1 were found to activate plasminogen at a rate up to 18-fold faster than B2CHO cells which are α5-deficient. This effect was dependent on the activation state of α5β1, as it was maximal in the presence of Mn2+. To determine the role of uPAR-α5β1 interactions in this effect, we determined the adhesion of these cells to immobilised soluble uPAR (suPAR). Neither cell-type was found to adhere to suPAR, but both cell types were found to adhere to an anti-uPAR monoclonal antibody in a uPAR- and integrin-dependent manner. This adhesion was 10-fold greater in the absence of α5β1, possibly implicating the involvement of non-α5-integrins. Soluble forms of the various components were used to investigate the molecular basis of these effects, but no direct interactions could be demonstrated between α5β1 and either uPAR, uPA or uPA-uPAR complex. This suggests that assembly of these components on the plasma membrane is required to influence uPAR function, increasing uPAR-dependent pericellular proteolysis and decreasing uPAR-dependent cell adhesion. These interactions may be modified by other integrins, suggesting a complex interplay between uPAR and integrins on the cell surface with the potential to regulate invasive cell migration.

scholarly journals Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis

2006 ◽  
Vol 203 (1) ◽  
pp. 189-201 ◽  
Author(s):  
Ronit Vogt Sionov ◽  
Orly Cohen ◽  
Shlomit Kfir ◽  
Yael Zilberman ◽  
Eitan Yefenof
Keyword(s):  
T Cell ◽  
Glucocorticoid Receptor ◽  
Cell Lines ◽  
Cell Types ◽  
Thymic Epithelial Cells ◽  
Dependent Manner ◽  
Localization Signal ◽  
Induced Apoptosis ◽  
T Cell Lines

The mechanisms by which glucocorticoid receptor (GR) mediates glucocorticoid (GC)-induced apoptosis are unknown. We studied the role of mitochondrial GR in this process. Dexamethasone induces GR translocation to the mitochondria in GC-sensitive, but not in GC-resistant, T cell lines. In contrast, nuclear GR translocation occurs in all cell types. Thymic epithelial cells, which cause apoptosis of the PD1.6 T cell line in a GR-dependent manner, induce GR translocation to the mitochondria, but not to the nucleus, suggesting a role for mitochondrial GR in eliciting apoptosis. This hypothesis is corroborated by the finding that a GR variant exclusively expressed in the mitochondria elicits apoptosis of several cancer cell lines. A putative mitochondrial localization signal was defined to amino acids 558–580 of human GR, which lies within the NH2-terminal part of the ligand-binding domain. Altogether, our data show that mitochondrial and nuclear translocations of GR are differentially regulated, and that mitochondrial GR translocation correlates with susceptibility to GC-induced apoptosis.

Role of LFA-1/ICAM-1-dependent cell adhesion in CD40-mediated inhibition of anti-IgM antibody-induced B-cell death

1995 ◽  
Vol 96 (6) ◽  
pp. 1136-1144 ◽  
Author(s):  
M MAYUMI ◽  
S SUMIMOTO ◽  
Y OHSHIMA ◽  
K KATAMURA ◽  
T HEIKE ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Adhesion ◽  
B Cell ◽  
Igm Antibody ◽  
Dependent Cell

scholarly journals Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation

2020 ◽  
Vol 21 (4) ◽  
pp. 1274
Author(s):  
Hideka Saotome ◽  
Atsumi Ito ◽  
Atsushi Kubo ◽  
Masafumi Inui
Keyword(s):  
Cell Types ◽  
Live Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Post Translational Modifications ◽  
Extracellular Signal ◽  
Multiple Cell ◽  
Sox9 Activity ◽  
Reporter Signal

Sox9 is a master transcription factor for chondrogenesis, which is essential for chondrocyte proliferation, differentiation, and maintenance. Sox9 activity is regulated by multiple layers, including post-translational modifications, such as SUMOylation. A detection method for visualizing the SUMOylation in live cells is required to fully understand the role of Sox9 SUMOylation. In this study, we generated a quantitative reporter for Sox9 SUMOylation that is based on the NanoBiT system. The simultaneous expression of Sox9 and SUMO1 constructs that are conjugated with NanoBiT fragments in HEK293T cells induced luciferase activity in SUMOylation target residue of Sox9-dependent manner. Furthermore, the reporter signal could be detected from both cell lysates and live cells. The signal level of our reporter responded to the co-expression of SUMOylation or deSUMOylation enzymes by several fold, showing dynamic potency of the reporter. The reporter was active in multiple cell types, including ATDC5 cells, which have chondrogenic potential. Finally, using this reporter, we revealed a extracellular signal conditions that can increase the amount of SUMOylated Sox9. In summary, we generated a novel reporter that was capable of quantitatively visualizing the Sox9-SUMOylation level in live cells. This reporter will be useful for understanding the dynamism of Sox9 regulation during chondrogenesis.

scholarly journals A new mouse model to study restoration of interleukin-6 (IL-6) expression in a Cre-dependent manner: microglial IL-6 regulation of experimental autoimmune encephalomyelitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Paula Sanchis ◽  
Olaya Fernández-Gayol ◽  
Gemma Comes ◽  
Kevin Aguilar ◽  
Anna Escrig ◽  
...  
Keyword(s):  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Interleukin 6 ◽  
Clinical Symptoms ◽  
Recovery Of Function ◽  
Cell Types ◽  
Dependent Manner ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Abstract Background Interleukin-6 (IL-6) is a pleiotropic cytokine that controls numerous physiological processes both in basal and neuroinflammatory conditions, including the inflammatory response to experimental autoimmune encephalomyelitis (EAE). IL-6 is produced by multiple peripheral and central cells, and until now, the putative roles of IL-6 from different cell types have been evaluated through conditional cell-specific IL-6 knockout mice. Nevertheless, these mice probably undergo compensatory responses of IL-6 from other cells, which makes it difficult to assess the role of each source of IL-6. Methods To give some insight into this problem, we have produced a novel mouse model: a conditional reversible IL-6 KO mouse (IL6-DIO-KO). By using double-inverted, open-reading-frame (DIO) technology, we created a mouse line with the loss of Il6 expression in all cells that can be restored by the action of Cre recombinase. Since microglia are one of the most important sources and targets of IL-6 into the central nervous system, we have recovered microglial Il6 expression in IL6-DIO-KO mice through breeding to Cx3cr1-CreER mice and subsequent injection of tamoxifen (TAM) when mice were 10–16 weeks old. Then, they were immunized with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55) 7 weeks after TAM treatment to induce EAE. Clinical symptoms and demyelination, CD3 infiltration, and gliosis in the spinal cord were evaluated. Results IL6-DIO-KO mice were resistant to EAE, validating the new model. Restoration of microglial Il6 was sufficient to develop a mild version of EAE-related clinical symptoms and neuropathology. Conclusions IL6-DIO-KO mouse is an excellent model to understand in detail the role of specific cellular sources of IL-6 within a recovery-of-function paradigm in EAE.

scholarly journals Calcium-dependent cell-cell adhesion molecules common to hepatocytes and teratocarcinoma stem cells.

1983 ◽  
Vol 97 (3) ◽  
pp. 944-948 ◽  
Author(s):  
S I Ogou ◽  
C Yoshida-Noro ◽  
M Takeichi
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Cell Types ◽  
Surface Proteins ◽  
Calcium Dependent ◽  
Molecular Weights ◽  
Teratocarcinoma Cells ◽  
Dependent Cell ◽  
Molecular Constitution ◽  
Cell Cell

The molecules involved in Ca2+-dependent cell-cell adhesion systems (CDS) in mouse hepatocytes were characterized and compared with those in teratocarcinoma cells. Fab fragments of antibody raised against liver tissues (anti-liver) inhibited Ca2+-dependent aggregation of both liver and teratocarcinoma cells. A monoclonal antibody raised against teratocarcinoma CDS (ECCD-1) also inhibited the Ca2+-dependent aggregation of these two cell types equally. These antibodies induced disruption of cell-cell adhesion in monolayers of hepatocytes. Thus, CDS in these two cell types are not immunologically distinctive. Immunochemical analyses with these antibodies showed that CDS in both hepatocytes and teratocarcinoma cells involved at least two classes of cell surface proteins with molecular weights of 124,000 and 104,000. ECCD-1 selectively bound to hepatocytes but not to fibroblastic cells in liver cell cultures. Thus, the molecular constitution of CDS in hepatocytes and teratocarcinoma stem cells is identical. As ECCD-1 reacts with other classes of embryonic and fetal cells, the molecules identified here could have a major role in cell-cell adhesion in various tissues at any developmental stage of animals.

scholarly journals Synaptic processes and immune-related pathways implicated in Tourette Syndrome

2020 ◽  
Author(s):  
Fotis Tsetsos ◽  
Dongmei Yu ◽  
Jae Hoon Sul ◽  
Alden Y. Huang ◽  
Cornelia Illmann ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Ion Channel ◽  
Tourette Syndrome ◽  
Cell Types ◽  
Synaptic Signaling ◽  
Gene Set ◽  
Individual Level ◽  
Genome Wide ◽  
Additional Support

AbstractTourette Syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with Tourette Syndrome (TS) and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating Ligand-gated Ion Channel Signaling, Lymphocytic, and Cell Adhesion and Trans-synaptic Signaling processes. MAGMA analysis further supported the involvement of the Cell Adhesion and Trans-synaptic Signaling gene set. The Lympho-cytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of Ligand-gated Ion Channel Signaling reinforce the role of GABA in TS, while the association of Cell Adhesion and Trans-synaptic Signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders.

scholarly journals Glycosynapses: microdomains controlling carbohydrate-dependent cell adhesion and signaling

2004 ◽  
Vol 76 (3) ◽  
pp. 553-572 ◽  
Author(s):  
Senitiroh Hakomori
Keyword(s):  
Signal Transduction ◽  
Cell Adhesion ◽  
Lipid Raft ◽  
Plasma Membranes ◽  
Cell Types ◽  
Src Family Kinases ◽  
Dependent Cell ◽  
Membrane Components ◽  
Type 3

The concept of microdomains in plasma membranes was developed over two decades, following observation of polarity of membrane based on clustering of specific membrane components. Microdomains involved in carbohydrate-dependent cell adhesion with concurrent signal transduction that affect cellular phenotype are termed "glycosynapse". Three types of glycosynapse have been distinguished: "type 1" having glycosphingolipid associated with signal transducers (small G-proteins, cSrc, Src family kinases) and proteolipids; "type 2" having O-linked mucin-type glycoprotein associated with Src family kinases; and "type 3" having N-linked integrin receptor complexed with tetraspanin and ganglioside. Different cell types are characterized by presence of specific types of glycosynapse or their combinations, whose adhesion induces signal transduction to either facilitate or inhibit signaling. E.g., signaling through type 3 glycosynapse inhibits cell motility and differentiation. Glycosynapses are distinct from classically-known microdomains termed "caveolae", "caveolar membrane", or more recently "lipid raft", which are not involved in carbohydrate-dependent cell adhesion. Type 1 and type 3 glycosynapses are resistant to cholesterol-binding reagents, whereas structure and function of "caveolar membrane" or "lipid raft" are disrupted by these reagents. Various data indicate a functional role of glycosynapses during differentiation, development, and oncogenic transformation.

scholarly journals Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1675-1679 ◽  
Author(s):  
DS Snyder ◽  
JF Desforges
Keyword(s):  
Arachidonic Acid ◽  
Mononuclear Cells ◽  
Nordihydroguaiaretic Acid ◽  
Cell Types ◽  
Dependent Manner ◽  
Myristate Acetate ◽  
Human Erythropoietin ◽  
Dose Dependent

Abstract Lipoxygenase (LPO) metabolites of arachidonic acid participate in the activation and/or proliferation of a variety of cell types. In this study, we examined the role of LPO metabolites in controlling myelopoiesis and erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human whole blood or whole mononuclear cells from human bone marrow were cultured in methylcellulose in the presence of various growth factors. Conditioned media containing human colony stimulating factors (CSF) or the tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added along with an endogenous source of burst- promoting activity (BPA) to induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL for myeloid and erythroid colonies, respectively. MDC depleted of T cells were similarly inhibited by BW755C. Similar results were seen with two other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole. A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher concentrations. Indomethacin, at concentrations that inhibit cyclooxygenase, had no significant effect, either alone or in combination with the LPO inhibitors. These results suggest that certain LPO products may be important mediators of both CSF- and PMA-induced myelopoiesis, and of BPA/EPO-induced erythropoiesis.

scholarly journals The Mitochondrial Ca2+ Overload via Voltage-Gated Ca2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide

2020 ◽  
Vol 21 (2) ◽  
pp. 491
Author(s):  
Chinatsu Nakagawa ◽  
Manami Suzuki-Karasaki ◽  
Miki Suzuki-Karasaki ◽  
Toyoko Ochiai ◽  
Yoshihiro Suzuki-Karasaki
Keyword(s):  
Cell Types ◽  
Channel Blockers ◽  
Organosulfur Compounds ◽  
Dependent Manner ◽  
Diallyl Trisulfide ◽  
Anticancer Effect ◽  
Anticancer Effects ◽  
Allium Vegetables ◽  
Ph Conditions

Allium vegetables such as garlic (Allium sativum L.) are rich in organosulfur compounds that prevent human chronic diseases, including cancer. Of these, diallyl trisulfide (DATS) exhibits anticancer effects against a variety of tumors, including malignant melanoma. Although previous studies have shown that DATS increases intracellular calcium (Ca2+) in different cancer cell types, the role of Ca2+ in the anticancer effect is obscure. In the present study, we investigated the Ca2+ pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca2+ entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca2+-dependent manner. It also induced mitochondrial Ca2+ (Ca2+mit) overload through intracellular and extracellular Ca2+ fluxes independently of SOCE. Strikingly, acidification augmented Ca2+mit overload, and Ca2+ channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca2+mit overload caused by melittin. Finally, Ca2+ channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca2+mit overload via a non-SOCE, thereby displaying the anti-melanoma effect.

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