scholarly journals Phospholipase D activity is essential for actin localization and actin-based motility in Dictyostelium

2005 ◽  
Vol 389 (1) ◽  
pp. 207-214 ◽  
Author(s):  
Soha ZOUWAIL ◽  
Trevor R. PETTITT ◽  
Stephen K. DOVE ◽  
Margarita V. CHIBALINA ◽  
Dale J. POWNER ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Essential Role ◽  
Kinase Activity ◽  
Complete Loss ◽  
Complete Inhibition ◽  
Cellular Processes ◽  
Small Clusters ◽  
Actin Localization

PLD (phospholipase D) activity catalyses the generation of the lipid messenger phosphatidic acid, which has been implicated in a number of cellular processes, particularly the regulation of membrane traffic. In the present study, we report that disruption of PLD signalling causes unexpectedly profound effects on the actin-based motility of Dictyostelium. Cells in which PLD activity is inhibited by butan-1-ol show a complete loss of actin-based structures, accompanied by relocalization of F-actin into small clusters, and eventually the nucleus, without a visible fall in levels of F-actin. Addition of exogenous phosphatidic acid reverses the effects of butan-1-ol, confirming that these effects are caused by inhibition of PLD. Loss of motility correlates with complete inhibition of endocytosis and a reduction in phagocytosis. Inhibition of PLD caused a major decrease in the synthesis of PtdIns(4,5)P2, which could again be reversed by exogenously applied phosphatidic acid. Thus the essential role of PLD signalling in both motility and endocytosis appears to be mediated directly via regulation of PtdIns(4)P kinase activity. This implies that localized PLD-regulated synthesis of PtdIns(4,5)P2 is essential for Dictyostelium actin function.

scholarly journals Essential role of glucose transporter GLUT3 for post-implantation embryonic development

2008 ◽  
Vol 200 (1) ◽  
pp. 23-33 ◽  
Author(s):  
S Schmidt ◽  
A Hommel ◽  
V Gawlik ◽  
R Augustin ◽  
N Junicke ◽  
...  
Keyword(s):  
Essential Role ◽  
Glucose Transporter ◽  
Growth Arrest ◽  
Complete Loss ◽  
Transporter Gene ◽  
Wild Type ◽  
Post Implantation ◽  
Time Point

Deletion of glucose transporter geneSlc2a3(GLUT3) has previously been reported to result in embryonic lethality. Here, we define the exact time point of growth arrest and subsequent death of the embryo.Slc2a3−/−morulae and blastocysts developed normally, implantedin vivo, and formed egg-cylinder-stage embryos that appeared normal until day 6.0. At day 6.5, apoptosis was detected in the ectodermal cells ofSlc2a3−/−embryos resulting in severe disorganization and growth retardation at day 7.5 and complete loss of embryos at day 12.5. GLUT3 was detected in placental cone, in the visceral ectoderm and in the mesoderm of 7.5-day-old wild-type embryos. Our data indicate that GLUT3 is essential for the development of early post-implanted embryos.

scholarly journals Phospholipase D2 Mediates Acute Aldosterone Secretion in Response to Angiotensin II in Adrenal Glomerulosa Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2162-2170 ◽  
Author(s):  
Haixia Qin ◽  
Michael A. Frohman ◽  
Wendy B. Bollag
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Cell Surface ◽  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Cell Interior ◽  
Aldosterone Secretion ◽  
Phospholipase D2 ◽  
Glomerulosa Cells

In primary bovine adrenal glomerulosa cells, the signaling enzyme phospholipase D (PLD) is suggested to mediate priming, the enhancement of aldosterone secretion after pretreatment with and removal of angiotensin II (AngII), via the formation of persistently elevated diacylglycerol (DAG). To further explore PLD’s role in priming, glomerulosa cells were pretreated with an exogenous bacterial PLD. Using this approach, phosphatidic acid (PA) is generated on the outer, rather than the inner, leaflet of the plasma membrane. Although PA is not readily internalized, the PA is nonetheless rapidly hydrolyzed by cell-surface PA phosphatases to DAG, which efficiently flips to the inner leaflet and accesses the cell interior. Pretreatment with bacterial PLD resulted in priming upon subsequent AngII exposure, supporting a role of DAG in this process, because the increase in DAG persisted after exogenous PLD removal. To determine the PLD isoform mediating aldosterone secretion, and presumably priming, primary glomerulosa cells were infected with adenoviruses expressing GFP, PLD1, PLD2, or lipase-inactive mutants. Overexpressed PLD2 increased aldosterone secretion by approximately 3-fold over the GFP-infected control under basal conditions, with a significant enhancement to about 16-fold over the basal value upon AngII stimulation. PLD activity was also increased basally and upon stimulation with AngII. In contrast, PLD1 overexpression had little effect on aldosterone secretion, despite the fact that PLD activity was enhanced. In both cases, the lipase-inactive PLD mutants showed essentially no effect on PLD activity or aldosterone secretion. Our results suggest that PLD2 is the isoform that mediates aldosterone secretion and likely priming.

scholarly journals Phospholipase D in Phytophthora infestans and Its Role in Zoospore Encystment

2002 ◽  
Vol 15 (9) ◽  
pp. 939-946 ◽  
Author(s):  
Maita Latijnhouwers ◽  
Teun Munnik ◽  
Francine Govers
Keyword(s):  
Phytophthora Infestans ◽  
G Proteins ◽  
Phospholipase D ◽  
Kinase Activity ◽  
Mechanical Agitation ◽  
Protein Activator ◽  
Late Blight Pathogen ◽  
Stimulation Of

We show that differentiation of zoospores of the late blight pathogen Phytophthora infestans into cysts, a process called encystment, was triggered by both phosphatidic acid (PA) and the G-protein activator mastoparan. Mastoparan induced the accumulation of PA, indicating that encystment by mastoparan most likely acts through PA. Likewise, mechanical agitation of zoospores, which often is used to induce synchronized encystment, resulted in increased levels of PA. The levels of diacylglycerolpyrophosphate (DGPP), the phosphorylation product of PA, increased simultaneously. Also in cysts, sporangiospores, and mycelium, mastoparan induced increases in the levels of PA and DGPP. Using an in vivo assay for phospholipase D (PLD) activity, it was shown that the mastoparan-induced increase in PA was due to a stimulation of the activity of this enzyme. Phospholipase C in combination with diacylglycerol (DAG) kinase activity also can generate PA, but activation of these enzymes by mastoparan was not detected under conditions selected to highlight 32P-PA production via DAG kinase. Primary and secondary butanol, which, like mastoparan, have been reported to activate G-proteins, also stimulated PLD activity, whereas the inactive tertiary isomer did not. Similarly, encystment was induced by n- and sec-butanol but not by tert-butanol. Together, these results show that Phytophthora infestans contains a mastoparan- and bu-tanol-inducible PLD pathway and strongly indicate that PLD is involved in zoospore encystment. The role of G-proteins in this process is discussed.

scholarly journals The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle

2006 ◽  
Vol 103 (12) ◽  
pp. 4741-4746 ◽  
Author(s):  
T. A. Hornberger ◽  
W. K. Chu ◽  
Y. W. Mak ◽  
J. W. Hsiung ◽  
S. A. Huang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Phosphatidic Acid ◽  
Mechanical Activation ◽  
Phospholipase D ◽  
Mtor Signaling

scholarly journals Role of Phospholipase D in Pasteurella haemolytica Leukotoxin-Induced Increase in Phospholipase A2 Activity in Bovine Neutrophils

1999 ◽  
Vol 67 (8) ◽  
pp. 3768-3772 ◽  
Author(s):  
Zuncai Wang ◽  
Cyril R. Clarke ◽  
Kenneth D. Clinkenbeard
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Pasteurella Haemolytica ◽  
Time Dependent ◽  
Regulatory Interaction ◽  
Pneumonic Pasteurellosis ◽  
Transphosphatidylation Reaction ◽  
Bovine Neutrophils ◽  
Phospholipase A2 Activity

ABSTRACT The effects of Pasteurella haemolytica leukotoxin (LKT) on the activity of phospholipase D (PLD) and the regulatory interaction between PLD and phospholipase A2 (PLA2) were investigated in assays using isolated bovine neutrophils labeled with tritiated phospholipid substrates of the two enzymes. Exposure of [3H]lysophosphatidylcholine-labeled neutrophils to LKT caused concentration- and time-dependent production of phosphatidic acid (PA), the product of PLD. LKT-induced generation of PA was dependent on extracellular calcium. Both production of PA and metabolism of [3H]-arachidonate ([3H]AA)-labeled phospholipids by PLA2 were inhibited when ethanol was used to promote the alternative PLD-mediated transphosphatidylation reaction, resulting in the production of phosphatidylethanol rather than PA. The role of PA in regulation of PLA2 activity was then confirmed by means of an add-back experiment, whereby addition of PA in the presence of ethanol restored PLA2-mediated release of radioactivity from neutrophil membranes. Considering the involvement of chemotactic phospholipase products in the pathogenesis of pneumonic pasteurellosis, development and use of anti-inflammatory agents that inhibit LKT-induced activation of PLD and PLA2 may improve therapeutic management of the disease.

scholarly journals Blocking the Bromodomains Function Contributes to Disturbances in Alga Chara vulgaris Spermatids Differentiation

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1352
Author(s):  
Agnieszka Wojtczak
Keyword(s):  
Endoplasmic Reticulum ◽  
Essential Role ◽  
Developmental Stages ◽  
Chromatin Condensation ◽  
Ultrastructural Level ◽  
Prolonged Treatment ◽  
Chara Vulgaris ◽  
Cellular Processes ◽  
Early Stages

Bromodomain containing (BRD) proteins play an essential role in many cellular processes. The aim of this study was to estimate activity of bromodomains during alga Chara vulgaris spermatids differentiation. The effect of a bromodomain inhibitor, JQ1 (100 μM), on the distribution of individual stages of spermatids and their ultrastructure was studied. The material was Feulgen stained and analysed in an electron microscope. JQ1 caused shortening of the early stages of spermiogenesis and a reverse reaction at the later stages. Additionally, in the same antheridium, spermatids at distant developmental stages were present. On the ultrastructural level, chromatin fibril system disorders and significantly distended endoplasmic reticulum (ER) cisternae already at the early stages were observed. Many autolytic vacuoles were also visible. The ultrastructural disturbances intensified after prolonged treatment with JQ1. The obtained data show that JQ1 treatment led to changes in the spermatid number and disturbances in chromatin condensation and to cytoplasm reduction. The current studies show some similarities between C. vulgaris and mammals spermiogenesis. Taken together, these results suggest that JQ1 interferes with the spermatid differentiation on many interdependent levels and seems to induce ER stress, which leads to spermatid degeneration. Studies on the role of bromodomains in algae spermiogenesis have not been conducted so far.

Diacylglycerol generation in fluoride-treated neutrophils: involvement of phospholipase D

Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2746-2756
Author(s):  
D English ◽  
G Taylor ◽  
JG Garcia
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Superoxide Anion ◽  
Second Messenger ◽  
Complete Inhibition ◽  
Fluoride Ion ◽  
Extracellular Medium ◽  
Time Points ◽  
Acid Generation ◽  
Transphosphatidylation Reaction

Neutrophils exposed to fluoride ion (F-) respond with a delayed and sustained burst of superoxide anion release that is both preceded by and dependent on the influx of Ca2+ from the extracellular medium. The results of this study demonstrate a similarly delayed and sustained generation of 1,2-diglyceride in F(-)-treated neutrophils, over 90% of which was 1,2-diacylglycerol. Diacylglycerol generation was not dependent on the presence of extracellular Ca2+. Conversely, in contrast to results obtained with other agonists, removal of extracellular Ca2+ markedly potentiated synthesis of diacylglycerol in F(-)-treated neutrophils. This effect was accompanied by a corresponding decrease in the recovery of phosphatidic acid. In either the presence or absence of extracellular Ca2+, phosphatidic acid accumulated before diacylglycerol in F(-)-treated cells, suggesting the latter was derived from the former. Consistent with this hypothesis, the phosphatidic acid phosphohydrolase inhibitor, propranolol, suppressed generation of diacylglycerol as it potentiated the accumulation of phosphatidic acid in F(-)-treated neutrophils. This effect was observed both in the presence and absence of extracellular Ca2+. Moreover, high levels of propranolol (160 mumol/L) effected complete inhibition of diacylglycerol generation in F(-)-treated neutrophils with a corresponding increase in phosphatidic acid generation. Phosphatidylethanol accumulated in neutrophils stimulated with F- in the presence of ethanol. The extent of phosphatidylethanol accumulation at all time points after addition of F- corresponded to decreased levels of both phosphatidic acid and diacylglycerol, indicating that phosphatidylethanol was derived from the phospholipase D-catalysed transphosphatidylation reaction. The results indicate that F- activates a Ca(2+)-independent phospholipase D, which appears to be the major, if not sole, catalyst for both phosphatidic acid and diacylglycerol generation in F(-)-treated neutrophils. Ca2+, mobilized as a result of F- stimulation and possibly as a consequence of phospholipase D activation, exerts a profound effect on cellular second messenger levels by modulating the conversion of phosphatidic acid to diacylglycerol.

scholarly journals Arachidonic acid activates phospholipase D in human neutrophils; essential role of endogenous leukotriene B4and inhibition by adenosine A2Areceptor engagement

2003 ◽  
Vol 73 (4) ◽  
pp. 530-539 ◽  
Author(s):  
Sonya Grenier ◽  
Nicolas Flamand ◽  
Julie Pelletier ◽  
Paul H. Naccache ◽  
Pierre Borgeat ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase D ◽  
Essential Role ◽  
Human Neutrophils

scholarly journals The Multiple Faces of MNT and Its Role as a MYC Modulator

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4682
Author(s):  
Judit Liaño-Pons ◽  
Marie Arsenian-Henriksson ◽  
Javier León
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Repression ◽  
Cell Biology ◽  
Essential Role ◽  
Present Knowledge ◽  
Special Focus ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Tumor Cell Survival

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

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