Phospholipase D Stimulates Release of Nascent Secretory Vesicles from the trans-Golgi Network
Ye-Guang Chen,Anirban Siddhanta,Cary D. Austin,Scott M. Hammond,Tsung Chang Sung,Michael A. Frohman,Andrew J. Morris,Dennis Shields +7 more
TLDR
It is demonstrated that immunoaffinity-purified human PLD1 stimulated nascent secretory vesicle budding from the TGN and ARF-1 stimulated endogenous PLD activity in Golgi membranes approximately threefold and this activation correlated with its enhancement of vesicles budding.Abstract:
Phospholipase D (PLD) is a phospholipid hydrolyzing enzyme whose activation has been implicated in mediating signal transduction pathways, cell growth, and membrane trafficking in mammalian cells. Several laboratories have demonstrated that small GTP-binding proteins including ADP-ribosylation factor (ARF) can stimulate PLD activity in vitro and an ARF-activated PLD activity has been found in Golgi membranes. Since ARF-1 has also been shown to enhance release of nascent secretory vesicles from the TGN of endocrine cells, we hypothesized that this reaction occurred via PLD activation. Using a permeabilized cell system derived from growth hormone and prolactin-secreting pituitary GH3 cells, we demonstrate that immunoaffinity-purified human PLD1 stimulated nascent secretory vesicle budding from the TGN approximately twofold. In contrast, a similarly purified but enzymatically inactive mutant form of PLD1, designated Lys898Arg, had no effect on vesicle budding when added to the permeabilized cells. The release of nascent secretory vesicles from the TGN was sensitive to 1% 1-butanol, a concentration that inhibited PLD-catalyzed formation of phosphatidic acid. Furthermore, ARF-1 stimulated endogenous PLD activity in Golgi membranes approximately threefold and this activation correlated with its enhancement of vesicle budding. Our results suggest that ARF regulation of PLD activity plays an important role in the release of nascent secretory vesicles from the TGN.read more
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Book ChapterDOI
Chapter 144 – Phospholipase D
Wenjuan Su,Michael A. Frohman +1 more
TL;DR: Immune responses and tumorigenesis represent two key physiological areas for which PLD may be a good drug target through development of specific inhibitors, and play a role in immune function and cancer inhibition.
Book ChapterDOI
Genetic and Metabolic Determinants of Fatty Acid Chain Length and Desaturation, Their Incorporation into Lipid Classes and Their Effects on Risk of Vascular and Metabolic Disease
TL;DR: Fatty acid metabolism is the result of the complex interaction of synthesis, remodelling and b-oxidation with some minor lipid species being involved in signalling and other regulatory mechanisms.
Journal ArticleDOI
Neospora caninum: comparative gene expression profiling of Neospora caninum wild type and a temperature sensitive clone.
Robert W. Li,Wenbin Tuo +1 more
TL;DR: The results suggest that the down-regulated genes may be in part responsible for the reduced pathogenesis of NCts-8; further characterization of the regulated genes may aid in understanding of molecular basis of virulence and development of countermeasures against neosporosis.
Book ChapterDOI
Measuring Phospholipase D Activity in Insulin-Secreting Pancreatic β-Cells and Insulin-Responsive Muscle Cells and Adipocytes
TL;DR: In this article, the authors present methodologies for assessing cellular phospholipase D activity in secretagogue-stimulated insulin-secreting pancreatic beta-cells and also insulin stimulated adipocyte and muscle cells, two of the principal insulin-responsive cell types controlling blood glucose levels.
References
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Journal Article
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Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting
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TL;DR: Overexpression of VPS34p resulted in an increase in PI 3-kinase activity, and this activity was specifically precipitated with antisera to Vps34p.
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Phosphatidylcholine breakdown and signal transduction
TL;DR: PC hydrolysis by PLA2, PLC or PLD is a widespread response elicited by most growth factors, cytokines, neurotransmitters, hormones and other extracellular signals and the mechanisms can involve G-proteins, PKC, Ca2+ and tyrosine kinase activities.
Journal ArticleDOI
ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity
TL;DR: The current finding suggests that PLD activity plays a prominent role in the action of ARF and that ARF may be a key component in the generation of second messengers via phospholipase D.
Journal ArticleDOI
Phosphoinositides as Regulators in Membrane Traffic
TL;DR: Growing evidence suggests that phosphorylation-dephosphorylation of the polar heads of phosphoinositides in specific intracellular locations signals either the recruitment or the activation of proteins essential for vesicular transport.