Regulation of protein sorting at the TGN by plasma membrane receptor activation

2000 ◽  
Vol 113 (4) ◽  
pp. 741-748 ◽  
Author(s):  
M. Baldassarre ◽  
A. Dragonetti ◽  
P. Marra ◽  
A. Luini ◽  
C. Isidoro ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cathepsin D ◽  
Leukemia Cell ◽  
Receptor Activation ◽  
Leukemia Cell Line ◽  
Major Player ◽  
Plasma Membrane Receptor ◽  
Immature Form ◽  
Secretory Lysosomes ◽  
Normal Processing

We show that in the rat basophilic leukemia cell line RBL, the physiological stimulation of the IgE receptor or direct activation of PKC leads to the missorting of proteins to the plasma membrane, diverting them from their normal intracellular destination. This is demonstrated for two classes of proteins that are normally targeted to the secretory lysosomes via completely different mechanisms, i.e. proteoglycans and the aspartic protease cathepsin D. In the latter case, normal processing of the enzyme is also affected, leading to secretion of the immature form of cathepsin. The present study shows how completely different sorting mechanisms, such as those for delivering proteoglycans and cathepsin D to secretory lysosomes, might share common regulatory signals and are similarly affected when the levels of these signals are perturbed. Finally, protein kinase C appears to be a major player in the signal transduction pathways, leading to proteoglycan and cathepsin D missorting.

scholarly journals Dynamics of a Chemoattractant Receptor in Living Neutrophils during Chemotaxis

1999 ◽  
Vol 10 (4) ◽  
pp. 1163-1178 ◽  
Author(s):  
Guy Servant ◽  
Orion D. Weiner ◽  
Enid R. Neptune ◽  
John W. Sedat ◽  
Henry R. Bourne
Keyword(s):  
Plasma Membrane ◽  
Fluorescent Protein ◽  
Membrane Lipids ◽  
Leukemia Cell ◽  
Leading Edge ◽  
Relative Strength ◽  
Leukemia Cell Line ◽  
Anterior Pole ◽  
Apparent Increase ◽  
Green Fluorescent

Persistent directional movement of neutrophils in shallow chemotactic gradients raises the possibility that cells can increase their sensitivity to the chemotactic signal at the front, relative to the back. Redistribution of chemoattractant receptors to the anterior pole of a polarized neutrophil could impose asymmetric sensitivity by increasing the relative strength of detected signals at the cell’s leading edge. Previous experiments have produced contradictory observations with respect to receptor location in moving neutrophils. To visualize a chemoattractant receptor directly during chemotaxis, we expressed a green fluorescent protein (GFP)-tagged receptor for a complement component, C5a, in a leukemia cell line, PLB-985. Differentiated PLB-985 cells, like neutrophils, adhere, spread, and polarize in response to a uniform concentration of chemoattractant, and orient and crawl toward a micropipette containing chemoattractant. Recorded in living cells, fluorescence of the tagged receptor, C5aR–GFP, shows no apparent increase anywhere on the plasma membrane of polarized and moving cells, even at the leading edge. During chemotaxis, however, some cells do exhibit increased amounts of highly folded plasma membrane at the leading edge, as detected by a fluorescent probe for membrane lipids; this is accompanied by an apparent increase of C5aR–GFP fluorescence, which is directly proportional to the accumulation of plasma membrane. Thus neutrophils do not actively concentrate chemoattractant receptors at the leading edge during chemotaxis, although asymmetrical distribution of membrane may enrich receptor number, relative to adjacent cytoplasmic volume, at the anterior pole of some polarized cells. This enrichment could help to maintain persistent migration in a shallow gradient of chemoattractant.

scholarly journals Nox2 and Rac1 Regulate H2O2-Dependent Recruitment of TRAF6 to Endosomal Interleukin-1 Receptor Complexes

2006 ◽  
Vol 26 (1) ◽  
pp. 140-154 ◽  
Author(s):  
Qiang Li ◽  
Maged M. Harraz ◽  
Weihong Zhou ◽  
Liang N. Zhang ◽  
Wei Ding ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Interleukin 1 ◽  
Receptor Activation ◽  
Receptor Complex ◽  
Small Interfering Rnas ◽  
Cellular Mechanisms ◽  
Receptor Complexes ◽  
Endosomal Compartment ◽  
Plasma Membrane Receptor ◽  
Subcellular Compartmentalization

ABSTRACT Reactive oxygen species (ROS) generated by NADPH oxidases (Nox) have been implicated in the regulation of signal transduction. However, the cellular mechanisms that link Nox activation with plasma membrane receptor signaling remain poorly defined. We have found that Nox2-derived ROS influence the formation of an active interleukin-1 (IL-1) receptor complex in the endosomal compartment by directing the H2O2-dependent binding of TRAF6 to the IL-1R1/MyD88 complex. Clearance of both superoxide and H2O2 from within the endosomal compartment significantly abrogated IL-1β-dependent IKK and NF-κB activation. MyD88-dependent endocytosis of IL-1R1 following IL-1β binding was required for the redox-dependent formation of an active endosomal receptor complex competent for IKK and NF-κB activation. Small interfering RNAs to either MyD88 or Rac1 inhibited IL-1β induction of endosomal superoxide and NF-κB activation. However, MyD88 and Rac1 appear to be recruited independently to IL-1R1 following ligand stimulation. In this context, MyD88 binding was required for inducing endocytosis of IL-1R1 following ligand binding, while Rac1 facilitated the recruitment of Nox2 into the endosomal compartment and subsequent redox-dependent recruitment of TRAF6 to the MyD88/IL-1R1 complex. The identification of Nox-active endosomes helps explain how subcellular compartmentalization of redox signals can be used to direct receptor activation from the plasma membrane.

Biocompatibility assessment of type-II collagen and its polypeptide for tissue engineering: effect of collagen's molecular weight and glycoprotein content on tumor necrosis factor (Fas/Apo-1) receptor activation in human acute T-lymphocyte leukemia cell line

RSC Advances ◽  
2016 ◽  
Vol 6 (17) ◽  
pp. 14236-14246 ◽  
Author(s):  
E. Jeevithan ◽  
Z. Jingyi ◽  
B. Bao ◽  
W. Shujun ◽  
R. JeyaShakila ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Leukemia Cell ◽  
Death Receptor ◽  
Type Ii Collagen ◽  
Receptor Activation ◽  
Leukemia Cell Line ◽  
Low Molecular Weight ◽  
Type Ii ◽  
Line P ◽  
Necrosis Factor

Fas cell surface death receptor activation by low molecular weight (57, 40 and 25 kDa) collagens was investigated based on MW and glycoprotein content.

scholarly journals Tricin Isolated from Enzyme-Treated Zizania latifolia Extract Inhibits IgE-Mediated Allergic Reactions in RBL-2H3 Cells by Targeting the Lyn/Syk Pathway

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2084
Author(s):  
Jae-Yeul Lee ◽  
Se-Ho Park ◽  
Kwang-Hwan Jhee ◽  
Seun-Ah Yang
Keyword(s):  
Protein Kinase ◽  
Leukemia Cell ◽  
Receptor Activation ◽  
Skin Aging ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 4 ◽  
Leukemia Cell Line ◽  
Zizania Latifolia ◽  
Mitogen Activated Protein ◽  
Regulatory Effects

Tricin, a flavone present in rice bran, is confirmed as the major efficacious compound present in the enzyme-treated Zizania latifolia extract (ETZL), which protects against UVB-induced skin-aging. However, the suppressive mechanism of tricin on allergic responses remains unknown. The present study, therefore, aimed to determine the mechanisms of tricin and ETZL on mast cell degranulation in IgE-activated rat basophilic leukemia cell line (RBL-2H3) cells. We investigated the regulatory effects of tricin and ETZL on degranulation, production of cytokines and lipid mediators, and signaling proteins involved in the IgE-bound high-affinity IgE receptor activation, mitogen-activated protein kinase, arachidonic acid and Syk. The production of β–hexosaminidase, tumor necrosis factor-α, interleukin-4, leukotrienes (LT) B4, LTC4 and prostaglandin E2 in IgE-stimulated RBL-2H3 cells were significantly inhibited by exposure to tricin or ETZL. Moreover, tricin and ETZL inhibit the phosphorylation of cytosolic phospholipase A2, 5-lipoxygenase and cyclooxygenase-2. Furthermore, the phosphorylation of Akt, ERK, p38, JNK, protein kinase Cδ and phospholipase Cγ1 were effectively suppressed by both samples. Exposure to tricin or ETZL also significantly decreases the phosphorylation of Lyn and Syk, but has minimal effect on Fyn. Taken together, our data indicate that tricin and ETZL are potential anti-allergic materials that could be applied for the prevention of allergy-related diseases.

scholarly journals Defective insulin receptor activation and altered lipid rafts in Niemann–Pick type C disease hepatocytes

2005 ◽  
Vol 391 (3) ◽  
pp. 465-472 ◽  
Author(s):  
Saara Vainio ◽  
Igor Bykov ◽  
Martin Hermansson ◽  
Eija Jokitalo ◽  
Pentti Somerharju ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Receptor ◽  
Lipid Rafts ◽  
Plasma Membranes ◽  
Cholesterol Content ◽  
Receptor Activation ◽  
Membrane Lipid ◽  
Plasma Membrane Receptor ◽  
Type C ◽  
Niemann Pick

Niemann–Pick type C (NPC) disease is a neuro-visceral cholesterol storage disorder caused by mutations in the NPC-1 or NPC-2 gene. In the present paper, we studied IR (insulin receptor) activation and the plasma-membrane lipid assembly in primary hepatocytes from control and NPC1–/– mice. We have previously reported that, in hepatocytes, IR activation is dependent on cholesterol–sphingolipid rafts [Vainio, Heino, Mansson, Fredman, Kuismanen, Vaarala and Ikonen (2002) EMBO Rep. 3, 95–100]. We found that, in NPC hepatocytes, IR levels were up-regulated and the receptor activation was compromised. Defective IR activation was reproduced in isolated NPC plasma-membrane preparations, which displayed an increased cholesterol content and saturation of major phospholipids. The NPC plasma membranes were less fluid than control membranes as indicated by increased DPH (1,6-diphenyl-1,3,5-hexatriene) fluorescence anisotropy values. Both in NPC hepatocytes and plasma-membrane fractions, the association of IR with low-density DRMs (detergent-resistant membranes) was increased. Moreover, the detergent resistance of both cholesterol and phosphatidylcholine were increased in NPC membranes. Finally, cholesterol removal inhibited IR activation in control membranes but restored IR activation in NPC membranes. Taken together, the results reveal a lipid imbalance in the NPC hepatocyte, which increases lipid ordering in the plasma membrane, alters the properties of lipid rafts and interferes with the function of a raft-associated plasma-membrane receptor. Such a mechanism may participate in the pathogenesis of NPC disease and contribute to insulin resistance in other disorders of lipid metabolism.

scholarly journals Characterization of a vitamin D3-resistant human chronic myelogenous leukemia cell line

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4283-4294 ◽  
Author(s):  
SR Lasky ◽  
MR Posner ◽  
K Iwata ◽  
A Santos-Moore ◽  
A Yen ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cell Line ◽  
Chronic Myelogenous Leukemia ◽  
Vitamin D3 ◽  
Leukemia Cell ◽  
Receptor Activation ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Chronic Myelogenous Leukemia Cell ◽  
D3 Receptors

A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is resistant to the antiproliferative effects of vitamin D3 was established. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D3, the resistant cells (JMRD3) continue to proliferate in the presence of 100 nmol/L vitamin D3. Both cells express similar patterns of differentiation-specific antigens after treatment with vitamin D3, and both express the retinoblastoma gene product (p110Rb). Vitamin D3 treatment of the sensitive RWLeu-4 cells decreased the level of the p110Rb protein, as well as its phosphorylation. In contrast, vitamin D3 treatment of JMRD3 had no effect on p110Rb expression or phosphorylation. Both RWLeu-4 and JMRD3 express similar vitamin D3 receptors and vitamin D3-inducible enzyme activities. Differences were detected in the DNA binding characteristics of the vitamin D3 receptors as determined by electrophoretic mobility shift studies. However, sequence analysis of the DNA-binding domain and immunoblot analysis showed no differences in the receptors. We conclude that some process subsequent to vitamin D3 receptor activation is altered in JMRD3 that partially separates vitamin D3-induced inhibition of proliferation from the induction of differentiation.

Intracellular Storage and Regulated Plasma Membrane Expression of Human Complement Receptor Type 1 in Rat Basophil Leukemia Cell Transfectants

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 300-309 ◽  
Author(s):  
Carolina Jost ◽  
Lloyd Klickstein ◽  
Erica Wetzler ◽  
Anoopa Kumar ◽  
Melvin Berger
Keyword(s):  
Plasma Membrane ◽  
Cell Activation ◽  
Leukemia Cell ◽  
Polymorphonuclear Neutrophils ◽  
Receptor Type ◽  
Leukemia Cell Line ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Complement Receptor Type 1

Polymorphonuclear neutrophils (PMN) contain multiple distinct secretory compartments that are sequentially mobilized during cell activation. Complement receptor type 1 (CR1) is a marker for a readily mobilizable secretory vesicle compartment, which can undergo exocytic fusion with the plasma membrane independently of secretion of traditional granule contents. The basis for the formation of these distinct compartments is incompletely understood. Primary and secondary granules are generated directly from the Golgi complex during different stages of development of the cell, obviating the need for sorting signals for proper packaging of their constituents. To determine whether the secretory vesicles are formed in a similar manner, we studied a stable rat basophilic leukemia cell line (RBL-CR1) transfected with a plasmid containing the cDNA of human CR1 driven by a viral promoter. The CR1 was present primarily intracellularly in small vesicles resembling the CR1 storage pools in resting PMN. Activation of RBL-CR1 resulted in translocation of intracellular CR1 to the plasma membrane, with mobilization requirements different from those of the classical RBL granules. Thus, in RBL-CR1, continuously synthesized CR1 is stored and upregulated in much the same way as in PMN. This suggests that differential timing of gene expression is not essential for proper storage of CR1 and that other sorting mechanisms are involved, which can be studied in RBL-transfectants.

Characteristics of insulin receptors and insulin action in human myelogenous leukemia cell line K-562

Diabetes ◽  
1985 ◽  
Vol 34 (4) ◽  
pp. 347-352 ◽  
Author(s):  
T. Yamanouchi ◽  
T. Tsushima ◽  
Y. Akanuma ◽  
M. Kasuga ◽  
H. Mizoguchi ◽  
...  
Keyword(s):  
Cell Line ◽  
Insulin Action ◽  
Leukemia Cell ◽  
Insulin Receptors ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line
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