scholarly journals Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

2000 ◽  
Vol 346 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Gemma WAY ◽  
Niamh O'LUANAIGH ◽  
Shamshad COCKCROFT
Keyword(s):  
Mast Cells ◽  
Phospholipase D ◽  
Protein Interactions ◽  
Cross Linking ◽  
Ige Receptor ◽  
Local Synthesis ◽  
Adp Ribosylation ◽  
Phosphatidylinositol Transfer ◽  
Lipid Protein Interactions ◽  
Adp Ribosylation Factor

The physiological stimulus to exocytosis in mast cells is the cross-linking of the high-affinity IgE receptor, FcϵR1, with antigen. We demonstrate a novel function for ADP-ribosylation factor 1 (ARF1) in the regulation of antigen-stimulated secretion using cytosol-depleted RBL-2H3 mast cells for reconstitution of secretory responses. When antigen is used as the stimulus, ARF1 also reconstitutes phospholipase D activation. Using ethanol to divert the phosphatidic acid (the product of phospholipase D activity) to phosphatidylethanol causes inhibition of ARF1-reconstituted secretion. In addition. ARF1 causes an increase in phosphatidylinositol 4,5-bisphosphate (PIP2) levels at the expense of phosphatidylinositol 4-monophosphate. The requirement for PIP2 in exocytosis was confirmed by using phosphatidylinositol transfer protein (PITPα) to increase PIP2 levels. Exocytosis, restored by either ARF1 or PITPα, was inhibited when PIP2 levels were depleted by phospholipase C∆1. We conclude that the function of ARF1 and PITPα is to increase the local synthesis of PIP2, the function of which in exocytosis is likely to be linked to lipid-protein interactions, whereby recruitment of key components of the exocytotic machinery are targeted to the appropriate membrane compartment.

Activity of Specific Lipid-regulated ADP Ribosylation Factor-GTPase–activating Proteins Is Required for Sec14p-dependent Golgi Secretory Function in Yeast

2002 ◽  
Vol 13 (7) ◽  
pp. 2193-2206 ◽  
Author(s):  
Lora L. Yanagisawa ◽  
Jennifer Marchena ◽  
Zhigang Xie ◽  
Xinmin Li ◽  
Pak P. Poon ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Phospholipase D ◽  
Protein Trafficking ◽  
Phosphoinositide Metabolism ◽  
Adp Ribosylation ◽  
Transfer Protein ◽  
Gtpase Activating Proteins ◽  
Pathway Function ◽  
Phosphatidylinositol Transfer ◽  
Adp Ribosylation Factor

Yeast phosphatidylinositol transfer protein (Sec14p) coordinates lipid metabolism with protein-trafficking events. This essential Sec14p requirement for Golgi function is bypassed by mutations in any one of seven genes that control phosphatidylcholine or phosphoinositide metabolism. In addition to these “bypass Sec14p” mutations, Sec14p-independent Golgi function requires phospholipase D activity. The identities of lipids that mediate Sec14p-dependent Golgi function, and the identity of the proteins that respond to Sec14p-mediated regulation of lipid metabolism, remain elusive. We now report genetic evidence to suggest that two ADP ribosylation factor-GTPase–activating proteins (ARFGAPs), Gcs1p and Age2p, may represent these lipid-responsive elements, and that Gcs1p/Age2p act downstream of Sec14p and phospholipase D in both Sec14p-dependent and Sec14p-independent pathways for yeast Golgi function. In support, biochemical data indicate that Gcs1p and Age2p ARFGAP activities are both modulated by lipids implicated in regulation of Sec14p pathway function. These results suggest ARFGAPs are stimulatory factors required for regulation of Golgi function by the Sec14p pathway, and that Sec14p-mediated regulation of lipid metabolism interfaces with the activity of proteins involved in control of the ARF cycle.

scholarly journals The emerging role of mast cell proteases in asthma

2019 ◽  
Vol 54 (4) ◽  
pp. 1900685 ◽  
Author(s):  
Gunnar Pejler
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Current Knowledge ◽  
Secretory Granules ◽  
Cross Linking ◽  
Lysosomal Hydrolases ◽  
Ige Receptor ◽  
Deficient Mice ◽  
Lines Of Evidence

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.

scholarly journals CD203c is Overexpressed on Neoplastic Mast Cells in Systemic Mastocytosis and is Upregulated upon IgE Receptor Cross-Linking

2008 ◽  
Vol 21 (4) ◽  
pp. 797-806 ◽  
Author(s):  
A.W. Hauswirth ◽  
L. Escribano ◽  
A. Prados ◽  
R. Nuñez ◽  
I. Mirkina ◽  
...  
Keyword(s):  
Mast Cells ◽  
Surface Antigen ◽  
Systemic Mastocytosis ◽  
Mrna Level ◽  
Surface Expression ◽  
Pcr Analysis ◽  
Cross Linking ◽  
Ige Receptor ◽  
Kit Ligand ◽  
Mast Cell Leukemia

The ectoenzyme E-NPP3 (CD203c) has recently been identified as a novel activation-linked cell surface antigen on basophils. In the present study, we examined expression of CD203c on normal mast cells (MC) and bone marrow (bm) MC derived from 85 patients with systemic mastocytosis (SM), including cases with indolent SM (ISM, n=72), SM with associated clonal hematologic non-MC-lineage disease (SM-AHNMD, n=6), aggressive SM (ASM, n=3), and mast cell leukemia (MCL, n=4). Surface expression of CD203c was analyzed by multicolor flow cytometry. In patients with SM, bm MC expressed significantly higher amounts of CD203c compared to normal bm MC (median MFI in controls: 260 versus median MFI in SM: 516, p<0.05). Slightly lower amounts of CD203c were detected on MC in SM-AHNMD and ASM compared to ISM. To demonstrate CD203c expression in MC at the mRNA level, neoplastic MC were highly enriched by cell sorting, and were found to express CD203c mRNA in RT-PCR analysis. Cross-linking of the IgE receptor on MC resulted in a substantial upregulation of CD203c, whereas the KIT-ligand stem cell factor (SCF) showed no significant effects. In conclusion, CD203c is a novel activation-linked surface antigen on MC that is upregulated in response to IgE receptor cross-linking and is overexpressed on neoplastic MC in patients with SM.

scholarly journals ADP-ribosylation Factor Proteins Mediate Agonist-induced Activation of Phospholipase D

1998 ◽  
Vol 273 (46) ◽  
pp. 30836-30841 ◽  
Author(s):  
Kuntala Shome ◽  
Yimin Nie ◽  
Guillermo Romero
Keyword(s):  
Phospholipase D ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor

scholarly journals Nuclear ADP-ribosylation Factor (ARF)- and Oleate-dependent Phospholipase D (PLD) in Rat Liver Cells

1997 ◽  
Vol 272 (8) ◽  
pp. 5208-5213 ◽  
Author(s):  
Yoshiko Banno ◽  
Keiko Tamiya-Koizumi ◽  
Hideko Oshima ◽  
Akemi Morikawa ◽  
Shonen Yoshida ◽  
...  
Keyword(s):  
Rat Liver ◽  
Phospholipase D ◽  
Liver Cells ◽  
Adp Ribosylation ◽  
Rat Liver Cells ◽  
Adp Ribosylation Factor

scholarly journals ADP-ribosylation-factor-regulated phospholipase D activity localizes to secretory vesicles and mobilizes to the plasma membrane following N-formylmethionyl-leucyl-phenylalanine stimulation of human neutrophils

1997 ◽  
Vol 325 (3) ◽  
pp. 581-585 ◽  
Author(s):  
C. P. MORGAN ◽  
H. SENGELOV ◽  
J. WHATMORE ◽  
N. BORREGAARD ◽  
S. COCKCROFT
Keyword(s):  
Plasma Membrane ◽  
Phospholipase D ◽  
Small Gtpases ◽  
Human Neutrophils ◽  
Secretory Vesicles ◽  
Rho Proteins ◽  
Adp Ribosylation ◽  
Activated Neutrophils ◽  
Adp Ribosylation Factor ◽  
Stimulation Of

Phospholipase D (PLD) is responsible for the hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. Human neutrophils contain PLD activity which is regulated by the small GTPases, ADP-ribosylation factor (ARF) and Rho proteins. In this study we have examined the subcellular localization of the ARF-regulated PLD activity in non-activated neutrophils and cells ‘primed‘ with N-formylmethionyl-leucyl-phenylalanine (fMetLeuPhe). We report that PLD activity is localized at the secretory vesicles in control cells and is mobilized to the plasma membrane upon stimulation with fMetLeuPhe. We conclude that the ARF-regulated PLD activity is translocated to the plasma membrane by secretory vesicles upon stimulation of neutrophils with fMetLeuPhe in inflammatory/priming doses. We propose that this relocalization of PLD is important for the subsequent events occurring during neutrophil activation.

ADP-Ribosylation Factor-Dependent Phospholipase D Activation by VPAC Receptors and a PAC1 Receptor Splice Variant

2001 ◽  
Vol 59 (6) ◽  
pp. 1523-1532 ◽  
Author(s):  
Derek A. McCulloch ◽  
Eve M. Lutz ◽  
Melanie S. Johnson ◽  
Derek N. Robertson ◽  
Chris J. MacKenzie ◽  
...  
Keyword(s):  
Phospholipase D ◽  
Splice Variant ◽  
Pac1 Receptor ◽  
Adp Ribosylation ◽  
Vpac Receptors ◽  
Adp Ribosylation Factor
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