Phospholipase D1 and Potential Targets of Its Hydrolysis Product, Phosphatidic Acid

ChemInform ◽  
2003 ◽  
Vol 34 (28) ◽  
Author(s):  
N. T. Ktistakis ◽  
C. Delon ◽  
M. Manifava ◽  
E. Wood ◽  
I. Ganley ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Hydrolysis Product ◽  
Phospholipase D1

Phospholipase D1 and potential targets of its hydrolysis product, phosphatidic acid

2003 ◽  
Vol 31 (1) ◽  
pp. 94-97 ◽  
Author(s):  
N.T. Ktistakis ◽  
C. Delon ◽  
M. Manifava ◽  
E. Wood ◽  
I. Ganley ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Hydrolysis Product ◽  
Ph Domain ◽  
Novel Proteins ◽  
Fatty Acylation ◽  
Px Domain ◽  
Phospholipase D1 ◽  
Sphingosine 1 Phosphate ◽  
Phox Homology ◽  
Adp Ribosylation Factor

Phospholipase D (PLD) hydrolyses phosphatidylcholine into phosphatidic acid (PA) and choline. Our work aims to understand the properties of PLD1, and to identify downstream targets of PA. In one set of projects, we have focused on membrane-targeting mechanisms and have proposed a hierarchy of signals that allows PLD1 to localize to intracellular membranes. These signals involve a functional pleckstrin homology (PH) domain and its fatty acylation on two adjacent cysteine residues. A nearby Phox homology (PX) domain may modulate the function of the fatty acylated PH domain. This complex array of signals is probably necessitated by the targeting of PLD1 to multiple endocytic and secretory membranes under basal and signal-dependent conditions. In another set of projects, we have used chemically synthesized PA coupled to a solid support in order to identify proteins that interact with this phospholipid. Several proteins have emerged from this screen as potential targets. Some (e.g. ADP-ribosylation factor, coatomer β subunit) are involved in trafficking and their PA affinity can be understood in terms of their regulated cycling on and off membranes during rounds of transport. Others (sphingosine 1-phosphate kinase and PtdIns4P 5-kinase) are implicated in pathways that also involve PLD activation. Others still are novel proteins (brain-specific neurochondrin) whose affinity for PA may contribute to an understanding of their cellular function.

Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4122-4128 ◽  
Author(s):  
Tomohiro Hitomi ◽  
Juan Zhang ◽  
Liliana M. Nicoletti ◽  
Ana Cristina G. Grodzki ◽  
Maria C. Jamur ◽  
...  
Keyword(s):  
Mast Cell ◽  
Phosphatidic Acid ◽  
Mast Cell Degranulation ◽  
Dominant Negative ◽  
Acid Formation ◽  
Wild Type ◽  
High Affinity ◽  
Phospholipase D1 ◽  
High Affinity Ige Receptor

Abstract To investigate the role of phospholipase D (PLD) in FcϵRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcϵRI stimulation resulted in the activation of both PLD1 and PLD2. However, PLD1 was the source of most of the receptor-induced PLD activity. There was enhanced FcϵRI-induced degranulation only in cells that overexpressed the catalytically inactive PLD1. This dominant-negative PLD1 enhanced FcϵRI-induced tyrosine phosphorylations of early signaling molecules such as the receptor subunits, Syk and phospholipase C-γ which resulted in faster release of Ca2+ from intracellular sources. Therefore, PLD1 negatively regulates signals upstream of the Ca2+ response. However, FcϵRI-induced PLD activation required Syk and was downstream of the Ca2+response, suggesting that basal PLD1 activity rather than that activated by cell stimulation controlled these early signaling events. Dominant-negative PLD1 reduced the basal phosphatidic acid formation in unstimulated cells, which was accompanied by an increase in FcϵRI within the lipid rafts. These results indicate that constitutive basal PLD1 activity by regulating phosphatidic acid formation controls the early signals initiated by FcϵRI aggregation that lead to mast cell degranulation. (Blood. 2004;104:4122-4128)

scholarly journals SNARE-catalyzed Fusion Events Are Regulated by Syntaxin1A–Lipid Interactions

2008 ◽  
Vol 19 (2) ◽  
pp. 485-497 ◽  
Author(s):  
Alice D. Lam ◽  
Petra Tryoen-Toth ◽  
Bill Tsai ◽  
Nicolas Vitale ◽  
Edward L. Stuenkel
Keyword(s):  
Phosphatidic Acid ◽  
Energy Barrier ◽  
Membrane Lipids ◽  
Specific Interaction ◽  
Lipid Binding ◽  
Snare Proteins ◽  
Fusion Pore ◽  
Lipid Interactions ◽  
Juxtamembrane Region ◽  
Phospholipase D1

Membrane fusion is a process that intimately involves both proteins and lipids. Although the SNARE proteins, which ultimately overcome the energy barrier for fusion, have been extensively studied, regulation of the energy barrier itself, determined by specific membrane lipids, has been largely overlooked. Our findings reveal a novel function for SNARE proteins in reducing the energy barrier for fusion, by directly binding and sequestering fusogenic lipids to sites of fusion. We demonstrate a specific interaction between Syntaxin1A and the fusogenic lipid phosphatidic acid, in addition to multiple polyphosphoinositide lipids, and define a polybasic juxtamembrane region within Syntaxin1A as its lipid-binding domain. In PC-12 cells, Syntaxin1A mutations that progressively reduced lipid binding resulted in a progressive reduction in evoked secretion. Moreover, amperometric analysis of fusion events driven by a lipid-binding–deficient Syntaxin1A mutant (5RK/A) demonstrated alterations in fusion pore dynamics, suggestive of an energetic defect in secretion. Overexpression of the phosphatidic acid–generating enzyme, phospholipase D1, completely rescued the secretory defect seen with the 5RK/A mutant. Moreover, knockdown of phospholipase D1 activity drastically reduced control secretion, while leaving 5RK/A-mediated secretion relatively unaffected. Altogether, these data suggest that Syntaxin1A–lipid interactions are a critical determinant of the energetics of SNARE-catalyzed fusion events.

Enhancement of Lysophosphatidic Acid-Induced ERK Phosphorylation by Phospholipase D1 via the Formation of Phosphatidic Acid

2001 ◽  
Vol 281 (5) ◽  
pp. 1337-1342 ◽  
Author(s):  
Jang-Hee Hong ◽  
Seo-Ok Oh ◽  
Michael Lee ◽  
Young-Rae Kim ◽  
Dong-Uk Kim ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Erk Phosphorylation ◽  
Phospholipase D1

scholarly journals The Coffin-Lowry Syndrome-Associated Protein RSK2 Regulates Neurite Outgrowth through Phosphorylation of Phospholipase D1 (PLD1) and Synthesis of Phosphatidic Acid

2013 ◽  
Vol 33 (50) ◽  
pp. 19470-19479 ◽  
Author(s):  
M.-R. Ammar ◽  
Y. Humeau ◽  
A. Hanauer ◽  
B. Nieswandt ◽  
M.-F. Bader ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Neurite Outgrowth ◽  
Phospholipase D1

scholarly journals Phospholipase D1‐induced phosphatidic acid at the plasma membrane promotes a late stage of large dense‐core

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Nicolas Vitale ◽  
Maria Zeniou‐Meyer ◽  
Sylvette Chasserot‐Golaz ◽  
Yannick Bailly ◽  
Marie‐France Bader
Keyword(s):  
Plasma Membrane ◽  
Phosphatidic Acid ◽  
Late Stage ◽  
Dense Core ◽  
Phospholipase D1

scholarly journals Phospholipase D1 Production of Phosphatidic Acid at the Plasma Membrane Promotes Exocytosis of Large Dense-core Granules at a Late Stage

2007 ◽  
Vol 282 (30) ◽  
pp. 21746-21757 ◽  
Author(s):  
Maria Zeniou-Meyer ◽  
Naama Zabari ◽  
Uri Ashery ◽  
Sylvette Chasserot-Golaz ◽  
Anne-Marie Haeberlé ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Phosphatidic Acid ◽  
Late Stage ◽  
Dense Core ◽  
Phospholipase D1 ◽  
Dense Core Granules
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